Trial Outcomes & Findings for Evaluation of Safety of Pomalidomide in Combination With Dexamethasone (Low Dose) in Patients With Refractory or Relapsed and Refractory Multiple Myeloma (NCT NCT01712789)

Last Updated: 2022-01-10

Results Overview

An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, regardless of etiology. Any worsening (i.e., any significant adverse change in the frequency or intensity of a pre- existing condition) was considered an AE. The severity of AEs were graded based on the symptoms according to version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs. A SAE = AE occurring at any dose that: * Results in death; * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

682 participants

Primary outcome timeframe

From the first dose of study treatment up to 28 days following the last dose of study treatment. The median duration of treatment with pomalidomide and LD-dex was 21.4 weeks.

Results posted on

2022-01-10

Participant Flow

The study was conducted at 112 sites: 4 in Austria, 7 in Belgium, 3 in Denmark, 1 in Estonia, 2 in Finland, 13 in France, 17 in Germany, 1 in Greece, 3 in Ireland, 15 in Italy, 5 in the Netherlands, 2 in Norway, 3 in Poland, 4 in Portugal, 1 in Slovakia, 15 in Spain, 2 in Sweden, 3 in Switzerland, 2 in Turkey, and 9 in the United Kingdom.

Study participants had to have either refractory or relapsed and refractory disease, defined as documented disease progression during or within 60 days of completing their last myeloma therapy to be eligible to participate in the trial.

Participant milestones

Participant milestones
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Overall Study STARTED	682
Overall Study Received Study Treatment	676
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	682

Reasons for withdrawal

Reasons for withdrawal
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Overall Study Lack of Efficacy	2
Overall Study Lost to Follow-up	1
Overall Study Progressive Disease	504
Overall Study Death	57
Overall Study Adverse Event	52
Overall Study Miscellaneous	31
Overall Study Withdrawal by Subject	21
Overall Study Transition to Commercial Treatment	8
Overall Study Participants Did Not Receive Study Drug	6

Baseline Characteristics

Evaluation of Safety of Pomalidomide in Combination With Dexamethasone (Low Dose) in Patients With Refractory or Relapsed and Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=682 Participants Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Age, Continuous	65.4 Years STANDARD_DEVIATION 9.10 • n=5 Participants
Sex: Female, Male Female	301 Participants n=5 Participants
Sex: Female, Male Male	381 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	52 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	626 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants
Race/Ethnicity, Customized White	669 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants
Race/Ethnicity, Customized Missing	4 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully active, no restrictions	295 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 = Restricted activity but ambulatory	319 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = Ambulatory and capable of all self-care	67 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 3 = Limited self-care	1 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 4 = Completely disabled	0 Participants n=5 Participants
Time since diagnosis	6.15 Years STANDARD_DEVIATION 3.649 • n=5 Participants
Beta 2 Microglobulin	5.48 mg/L STANDARD_DEVIATION 4.713 • n=5 Participants
Serum Light Chain Type Kappa	364 Participants n=5 Participants
Serum Light Chain Type Lambda	230 Participants n=5 Participants
Serum Light Chain Type No Serum Light chain Type Detected	16 Participants n=5 Participants
Serum Light Chain Type Test Not Performed	72 Participants n=5 Participants
Serum Heavy Chain Type Immunoglobulin A (IgA)	145 Participants n=5 Participants
Serum Heavy Chain Type Immunoglobulin D (IgD)	5 Participants n=5 Participants
Serum Heavy Chain Type Immunoglobulin E (IgE)	0 Participants n=5 Participants
Serum Heavy Chain Type Immunoglobulin G (IgG)	388 Participants n=5 Participants
Serum Heavy Chain Type Immunoglobulin M (IgM)	4 Participants n=5 Participants
Serum Heavy Chain Type No serum heavy chain type detected	68 Participants n=5 Participants
Serum Heavy Chain Type Test not performed	72 Participants n=5 Participants
Renal Function (Cockcroft Gault Creatinine Clearance) < 30 mL/min	12 Participants n=5 Participants
Renal Function (Cockcroft Gault Creatinine Clearance) 30 - < 45 mL/min	57 Participants n=5 Participants
Renal Function (Cockcroft Gault Creatinine Clearance) 45 - < 60 mL/min	168 Participants n=5 Participants
Renal Function (Cockcroft Gault Creatinine Clearance) 60 - < 80 mL/min	190 Participants n=5 Participants
Renal Function (Cockcroft Gault Creatinine Clearance) ≥ 80 mL/min	250 Participants n=5 Participants
Renal Function (Cockcroft Gault Creatinine Clearance) Missing	5 Participants n=5 Participants
Corrected Serum Calcium	2.43 mmol/L STANDARD_DEVIATION 0.231 • n=5 Participants

PRIMARY outcome

Timeframe: From the first dose of study treatment up to 28 days following the last dose of study treatment. The median duration of treatment with pomalidomide and LD-dex was 21.4 weeks.

Population: The safety population includes all enrolled participants who received at least one dose of the IP.

Outcome measures

Outcome measures
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=676 Participants Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Serious TEAE L/T Stopping of LD-Dex	34 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 Serious TEAE L/T Stopping either POM or LD-Dex	37 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE L/T to Stopping of POM	54 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE L/T to Stopping of LD-DEX	61 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE L/T to Stopping of Either POM or LD-DEX	63 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 Study Drug Related TEAE (L/T) Stopping POM	30 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 Study Drug Related TEAE L/T Stopping LD-Dex	19 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 Drug Related TEAE L/T Stopping LD-Dex or POM	38 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE L/T to Reduction (R/D) of POM	164 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE L/T to R/D of LD-DEX	150 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE L/T to R/D of Either POM or LD-DEX	244 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Study Drug Related TEAE L/T to R/D of POM	142 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Study Drug Related TEAE L/T to R/D of LD-DEX	135 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 StudyDrug Related TEAE L/T to R/D POM or LD-DEX	224 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE L/T to Interruption (I/R) of POM	455 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE L/T to I/R of LD-DEX	434 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE L/T to I/R of either POM or LD-DEX	470 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Study Drug Related TEAE L/T to I/R of POM	294 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Study Drug Related TEAE L/T to I/R of LD-DEX	185 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥1 StudyDrug Related TEAE L/T to I/R POM or LD-DEX	333 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ TEAE	673 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE Related to Pomalidomide (POM)	527 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE Related to LD-Dex	448 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 TEAE Related to Either POM or LD-Dex	575 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Grade (Gr) 3 or 4 TEAE	606 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Gr 3 or 4 TEAE Related to (R/T) POM	417 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Gr 3 or 4 TEAE R/T LD-Dex	226 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Gr 3 or 4 TEAE R/T Either POM or LD-Dex	448 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Grade 5 TEAE	127 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Grade 5 TEAE R/T POM	14 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Grade 5 TEAE R/T LD-Dex	16 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Grade 5 TEAE R/T either POM or LD-Dex	18 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Serious TEAE	448 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Serious TEAE R/T POM	187 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Serious TEAE R/T LD-Dex	146 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Serious TEAE R/T Either POM or LD-Dex	215 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAE) ≥ 1 Serious TEAE Leading to (L/T)Stopping of POM	36 Participants

SECONDARY outcome

Timeframe: Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks

Population: The intent to treat (ITT) population was defined as all enrolled participants (participants who received an interactive voice response system (IVRS) enrollment date) regardless of whether they received any investigational product (IP) or not.

Overall response rate (ORR) was defined as the percentage of participants with a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) according to the International Myeloma Working Group uniform response criteria (IMWG URC) assessed by the Investigator. Responses must have been confirmed at at least 2 consecutive assessments before the institution of any new therapy with no known evidence of progressive or new bone lesions

Outcome measures

Outcome measures
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=682 Participants Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Overall Response	33.4 Percentage of Participants Interval 29.9 to 37.1

SECONDARY outcome

Timeframe: Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks

Population: Includes participants with a response (sCR, VGPR or PR).

Time to response was defined as the time from treatment enrollment to the first documentation of response (sCR, CR, VGPR or PR) based on IMWG criteria.

Outcome measures

Outcome measures
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=228 Participants Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Time to Response	8.1 Weeks Interval 2.0 to 112.0

SECONDARY outcome

Timeframe: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months

Population: Includes participants with a response (sCR, VGPR or PR).

Duration of response, calculated for responders only, was defined as time from the initial documented response (SCR, CR, VGPR or PR) to the first confirmed disease progression, or death if no disease progression was recorded. Participants without a documented progression were censored at the time of their last tumor assessment.

Outcome measures

Outcome measures
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=228 Participants Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Kaplan Meier Estimate of Duration of Response	7.9 Months Interval 6.48 to 8.78

SECONDARY outcome

Timeframe: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months

Progression free survival was calculated as the time from study enrollment, defined as the IVRS enrollment date, until either PD or death (any cause). Participants without an event (either a documented PD or death) at the time of study end were censored at the time of their last documented disease assessment or at the IVRS enrollment date if no disease assessment was conducted.

Outcome measures

Outcome measures
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=682 Participants Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Kaplan Meier Estimate of Progression Free Survival (PFS) According to the European Medicines Agency Guidelines	4.6 Months Interval 3.91 to 4.9

SECONDARY outcome

Timeframe: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months

Time to progression was calculated as the time from study enrollment until first recorded disease progression as determined by the site investigator based on the IMWG criteria, or until death due to progression. Participants not experiencing a documented progression were censored at the time of their last tumor assessment (or at the time of trial enrollment if no assessment was conducted).

Outcome measures

Outcome measures
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=682 Participants Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Kaplan Meier Estimate of Time to Progression	4.8 Months Interval 4.27 to 5.56

SECONDARY outcome

Timeframe: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months

Overall survival was calculated as the time from study enrollment, defined as the IVRS enrollment date, until death due to any cause. Participants who did not have death data at the time of study end/analysis were censored at the time they were last known to be alive.

Outcome measures

Outcome measures
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=682 Participants Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Kaplan Meier Estimate of Overall Survival (OS)	11.9 Months Interval 10.65 to 13.41

SECONDARY outcome

Timeframe: Cycles 1, 2, 3, 4, 5, 6

Population: Pharmacokinetic population Pharmacokinetic samples from 476 participants included in studies CC-4047-MM-005 and CC 4047 MM 010 were used for the population PK analysis of pomalidomide

Pharmacokinetic (PK) parameters are derived from pomalidomide concentration versus time data.

Outcome measures

Outcome measures
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=476 Participants Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Pomalidomide Exposure - Apparent (Oral) Clearance (CL/F)	6.02 Liters/hour Interval 5.67 to 6.48

SECONDARY outcome

Timeframe: Cycles 1, 2, 3, 4, 5, 6

Population: Pharmacokinetic population Pharmacokinetic samples from 476 participants included in studies CC-4047-MM-005 and CC 4047 MM 010 were used for the population PK analysis of pomalidomide

Pharmacokinetic (PK) parameters are derived from Pomalidomide concentration versus time data.

Outcome measures

Outcome measures
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=476 Participants Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Pomalidomide Exposure - Apparent Volume of Distribution (V/F)	75.10 Liters Interval 63.57 to 89.17

SECONDARY outcome

Timeframe: Study entry

Population: Statistical analysis could not be performed due to high level of missing cytogenetic data as well as cytogenetic probe analysis being non- compliant with study requirements which lead to an inability to accurately identify specific cytogenetic abnormalities.

Cytogenetic analysis was to be performed using fluorescence in situ hybridization (FISH) methodology at a local laboratory, to evaluate the relationship between cytogenetic profiles and the combination of POM and LD-DEX in terms of response and outcome.

Outcome measures

Outcome data not reported

Adverse Events

Pomalidomide Plus Low Dose Dexamethasone (LD-Dex)

Serious events: 448 serious events

Other events: 646 other events

Deaths: 598 deaths

Serious adverse events

Serious adverse events
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=676 participants at risk Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Hepatobiliary disorders Hyperbilirubinaemia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Hepatobiliary disorders Liver disorder	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Immune system disorders Drug hypersensitivity	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Abdominal infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Abscess limb	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Anal abscess	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Appendicitis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Arthritis bacterial	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Atypical pneumonia	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Bacteraemia	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Bacterial diarrhoea	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Biliary sepsis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Bronchitis	1.3% 9/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Bronchopulmonary aspergillosis	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Bursitis infective	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Campylobacter gastroenteritis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Catheter site infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Cellulitis	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Cerebral aspergillosis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Citrobacter infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Clostridial sepsis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Clostridium difficile colitis	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Cystitis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Device related infection	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Diverticulitis	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Ear infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Erysipelas	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Escherichia infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Escherichia sepsis	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Escherichia urinary tract infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Folliculitis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Gastroenteritis	0.74% 5/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Gastroenteritis norovirus	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Herpes zoster infection neurological	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Infection	2.1% 14/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Influenza	0.74% 5/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Leishmaniasis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Listeria sepsis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Listeriosis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Localised infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Lower respiratory tract infection	3.3% 22/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Lung infection	2.4% 16/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Meningitis pneumococcal	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Meningococcal sepsis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Neutropenic sepsis	0.74% 5/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Oral fungal infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Oral infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Osteomyelitis bacterial	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Otitis externa	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Parainfluenzae virus infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pharyngitis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pneumococcal sepsis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pneumocystis jirovecii pneumonia	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pneumonia	17.3% 117/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pneumonia influenzal	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pneumonia pneumococcal	0.74% 5/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pneumonia respiratory syncytial viral	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pneumonia staphylococcal	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pneumonia streptococcal	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pneumonia viral	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pseudomonal sepsis	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pulmonary sepsis	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Respiratory moniliasis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Respiratory tract infection	1.6% 11/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Rhinovirus infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Sepsis	2.1% 14/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Septic shock	2.2% 15/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Sinusitis bacterial	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Soft tissue infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Staphylococcal infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Staphylococcal sepsis	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Staphylococcal skin infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Streptococcal bacteraemia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Streptococcal infection	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Systemic candida	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Systemic infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Tracheobronchitis	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Upper respiratory tract infection	1.2% 8/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Urinary tract infection	1.6% 11/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Urinary tract infection bacterial	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Urosepsis	0.74% 5/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Vascular device infection	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Ankle fracture	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Clavicle fracture	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Contusion	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Fall	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Febrile nonhaemolytic transfusion reaction	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Femoral neck fracture	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Femur fracture	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Head injury	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Humerus fracture	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Ilium fracture	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Joint dislocation	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Perineal injury	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Post-traumatic pain	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Rib fracture	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Spinal compression fracture	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Subdural haematoma	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations Protein urine present	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Tibia fracture	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Injury, poisoning and procedural complications Traumatic fracture	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations Blood creatinine increased	0.89% 6/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations Blood immunoglobulin A increased	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations C-reactive protein increased	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations International normalised ratio increased	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations Monoclonal immunoglobulin present	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations Neutrophil count decreased	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations Platelet count decreased	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations White blood cell count decreased	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Ruptured cerebral aneurysm	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Decreased appetite	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Dehydration	0.74% 5/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Hyperamylasaemia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Hypercalcaemia	4.4% 30/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Hyperglycaemia	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Hyperkalaemia	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Hypocalcaemia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Hypoglycaemia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Hypokalaemia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Hyponatraemia	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Metabolic acidosis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Tumour lysis syndrome	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Arthralgia	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Arthritis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Back pain	1.0% 7/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Bone lesion	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Bone pain	1.0% 7/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Neck pain	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Osteolysis	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Pain in extremity	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Pathological fracture	1.0% 7/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Spinal pain	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.89% 6/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal stromal tumour	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive breast carcinoma	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Monoclonal gammopathy	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell leukaemia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	1.5% 10/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	1.0% 7/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the tongue	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Cauda equina syndrome	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Cerebral haematoma	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Cognitive disorder	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Coma	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Depressed level of consciousness	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Disturbance in attention	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Encephalopathy	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Facial nerve disorder	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Generalised tonic-clonic seizure	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Haemorrhage intracranial	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Headache	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders IIIrd nerve paresis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Intracranial aneurysm	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Lateral medullary syndrome	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Motor dysfunction	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Paraesthesia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Paraplegia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Parkinsonism	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Peripheral motor neuropathy	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Peripheral sensorimotor neuropathy	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Presyncope	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Seizure	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Somnolence	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Spinal cord compression	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Subarachnoid haemorrhage	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Syncope	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Psychiatric disorders Confusional state	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Psychiatric disorders Depression	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Psychiatric disorders Disorientation	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Renal and urinary disorders Acute kidney injury	3.8% 26/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Renal and urinary disorders Crush syndrome	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Renal and urinary disorders Haematuria	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Renal and urinary disorders Nephrolithiasis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Renal and urinary disorders Oliguria	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Renal and urinary disorders Renal failure	3.4% 23/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Renal and urinary disorders Renal impairment	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Renal and urinary disorders Renal vascular thrombosis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Renal and urinary disorders Urinary retention	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Reproductive system and breast disorders Scrotal cyst	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Cough	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.2% 15/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.74% 5/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Orthopnoea	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.89% 6/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Productive cough	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.74% 5/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.74% 5/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.1% 14/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Skin and subcutaneous tissue disorders Rash	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Skin and subcutaneous tissue disorders Skin necrosis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Social circumstances Social stay hospitalisation	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Vascular disorders Aortic stenosis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Vascular disorders Deep vein thrombosis	0.89% 6/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Vascular disorders Haematoma	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Vascular disorders Hypertension	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Vascular disorders Hypotension	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Vascular disorders Shock haemorrhagic	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Anaemia	2.2% 15/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Bone marrow failure	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Febrile bone marrow aplasia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Febrile neutropenia	5.0% 34/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Heparin-induced thrombocytopenia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Hyperviscosity syndrome	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Leukopenia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Neutropenia	3.0% 20/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Pancytopenia	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Thrombocytopenia	1.9% 13/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Acute coronary syndrome	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Acute myocardial infarction	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Angina pectoris	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Atrial fibrillation	2.5% 17/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Atrial flutter	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Atrioventricular block	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Cardiac amyloidosis	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Cardiac arrest	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Cardiac disorder	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Cardiac failure	1.8% 12/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Cardiac failure congestive	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Cardio-respiratory arrest	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Coronary artery stenosis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Myocardial infarction	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Nodal arrhythmia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Palpitations	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Cardiac disorders Sinus bradycardia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Eye disorders Conjunctival haemorrhage	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Eye disorders Exophthalmos	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Abdominal pain	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Abdominal pain upper	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Anal fistula	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Constipation	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Diarrhoea	0.89% 6/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Diverticulum intestinal	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Gastritis	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Gastrointestinal amyloidosis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Haemorrhoids	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Ileus	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Intestinal infarction	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Large intestinal haemorrhage	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Large intestine perforation	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Nausea	0.44% 3/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Pancreatitis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Pancreatitis acute	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Rectal haemorrhage	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Rectal ulcer	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Volvulus	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Vomiting	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Asthenia	0.74% 5/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Death	0.59% 4/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Disease progression	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Euthanasia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Fatigue	0.74% 5/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders General physical health deterioration	6.7% 45/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Generalised oedema	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Hyperpyrexia	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Hyperthermia	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Malaise	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Mucosal inflammation	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Multiple organ dysfunction syndrome	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Non-cardiac chest pain	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Oedema	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Oedema peripheral	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Pain	0.30% 2/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Pyrexia	6.1% 41/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Hepatobiliary disorders Cholecystitis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Hepatobiliary disorders Cholecystitis acute	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Hepatobiliary disorders Cholelithiasis	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Hepatobiliary disorders Gallbladder obstruction	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Hepatobiliary disorders Hepatic failure	0.15% 1/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.

Other adverse events

Other adverse events
Measure	Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) n=676 participants at risk Participants received 4 mg pomalidomide (POM) by mouth (PO) on Days 1 to 21 of each 28-day treatment cycle and low dose dexamethasone (LD-Dex) PO at the starting dose of 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle until the documentation of confirmed progressive disease (PD), intolerable toxicity, death, withdrawal of participation in the study/consent, lost to follow-up, or as long as they benefited from therapy according to the opinion of the responsible study investigator.
Blood and lymphatic system disorders Anaemia	48.4% 327/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Leukopenia	13.6% 92/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Neutropenia	56.5% 382/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Blood and lymphatic system disorders Thrombocytopenia	34.9% 236/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Abdominal pain	5.0% 34/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Constipation	24.1% 163/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Diarrhoea	17.5% 118/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Nausea	14.2% 96/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Gastrointestinal disorders Vomiting	7.2% 49/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Asthenia	22.9% 155/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Fatigue	29.1% 197/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Oedema peripheral	16.0% 108/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
General disorders Pyrexia	26.3% 178/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Bronchitis	10.4% 70/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Nasopharyngitis	8.4% 57/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Pneumonia	5.6% 38/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Respiratory tract infection	8.6% 58/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Upper respiratory tract infection	7.4% 50/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Infections and infestations Urinary tract infection	8.0% 54/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations Blood creatinine increased	7.2% 49/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations C-reactive protein increased	5.0% 34/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations Neutrophil count decreased	7.0% 47/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Investigations Weight decreased	7.0% 47/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Decreased appetite	10.2% 69/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Hypercalcaemia	5.9% 40/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Hyperglycaemia	5.9% 40/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Metabolism and nutrition disorders Hypokalaemia	7.7% 52/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 42/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Back pain	15.5% 105/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Bone pain	9.6% 65/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Muscle spasms	14.2% 96/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Muscular weakness	5.2% 35/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	8.0% 54/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.5% 37/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Musculoskeletal and connective tissue disorders Pain in extremity	8.0% 54/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Dizziness	8.1% 55/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Headache	7.2% 49/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Peripheral sensory neuropathy	11.7% 79/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Nervous system disorders Tremor	6.7% 45/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Psychiatric disorders Confusional state	5.5% 37/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Psychiatric disorders Insomnia	11.2% 76/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Cough	20.9% 141/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.3% 117/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.0% 47/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.5% 37/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Skin and subcutaneous tissue disorders Pruritus	5.3% 36/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.
Skin and subcutaneous tissue disorders Rash	8.0% 54/676 • All-cause mortality is reported from enrollment until the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months. Adverse events are reported from first dose of study drug up to 28 days after last dose; median duration of treatment was 21.4 weeks. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is \> 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
Publication restrictions are in place

Restriction type: OTHER