Trial Outcomes & Findings for Carfilzomib in Combination With Dexamethasone (Kd) in Chinese Patients With Relapsed & Refractory Multiple Myeloma (NCT NCT03029234)

Last Updated: 2022-05-25

Results Overview

ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria. sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and \< 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC. VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein \<100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC). PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to \< 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

126 participants

Primary outcome timeframe

Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 5 November 2018; median follow-up time for progression was 8.9 months.

Results posted on

2022-05-25

Participant Flow

This study was conducted at 18 centers in China. The primary efficacy analysis was prespecified to occur when all enrolled participants had received 6 cycles of therapy or discontinued treatment. This occurred on November 5, 2018. A final analysis for efficacy was prespecified when all enrolled participants had the opportunity to be treated with at least 12 cycles. This occurred on March 15, 2019. The final analysis for safety occurred once all participants completed the study, 4 June 2021.

Participant milestones

Participant milestones
Measure	Carfilzomib With Dexamethasone Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Overall Study STARTED	126
Overall Study Received Carfilzomib	123
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	99

Reasons for withdrawal

Reasons for withdrawal
Measure	Carfilzomib With Dexamethasone Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Overall Study Sponsor Decision	1
Overall Study Withdrawal by Subject	5
Overall Study Death	91
Overall Study Lost to Follow-up	2

Baseline Characteristics

Participants with available data

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Carfilzomib With Dexamethasone n=123 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Age, Continuous	59.8 years STANDARD_DEVIATION 9.4 • n=123 Participants
Sex: Female, Male Female	56 Participants n=123 Participants
Sex: Female, Male Male	67 Participants n=123 Participants
Race/Ethnicity, Customized Asian	123 Participants n=123 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully active)	68 Participants n=123 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restricted but ambulatory)	45 Participants n=123 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 (Ambulatory but unable to work)	10 Participants n=123 Participants
Time From Initial Diagnosis to First Dose	38.70 months n=117 Participants • Participants with available data
Total Number of Prior Regimens	4.0 regimens n=123 Participants

PRIMARY outcome

Timeframe: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 5 November 2018; median follow-up time for progression was 8.9 months.

Population: Safety population

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=123 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee	35.8 percentage of participants Interval 27.3 to 44.9

SECONDARY outcome

Timeframe: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 10.3 months.

Population: Safety population

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=123 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Investigator	35.0 percentage of participants Interval 26.6 to 44.1

SECONDARY outcome

Timeframe: Response was assessed every 28 days until disease progression; ORR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.

Population: Safety population

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=123 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee	35.8 percentage of participants Interval 27.3 to 44.9

SECONDARY outcome

Population: Safety population

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=123 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Investigator	35.0 percentage of participants Interval 26.6 to 44.1

SECONDARY outcome

Timeframe: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 6 cycles or discontinued treatment; the data cut-off date was 05 November 2018; median follow-up time for progression was 8.9 months.

Population: Safety population

Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response). MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas is also required

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=123 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee	48.0 percentage of participants Interval 38.9 to 57.2

SECONDARY outcome

Population: Safety population

Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response). MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas was also required.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=123 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Investigator	46.3 percentage of participants Interval 37.3 to 55.6

SECONDARY outcome

Timeframe: Response was assessed every 28 days until disease progression; CBR was analyzed after all participants received at least 12 cycles or discontinued treatment; the data cut-off date was 15 March 2019; median follow-up time for progression was 12.8 months.

Population: Safety population

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=123 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee	48.0 percentage of participants Interval 38.9 to 57.2

SECONDARY outcome

Population: Safety population

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=123 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Investigator	46.3 percentage of participants Interval 37.3 to 55.6

SECONDARY outcome

Timeframe: Response was assessed every 28 days until disease progression; the data cut-off date was 15 March 2019; median follow-up time for progression assessed by independent review committee and by investigators were 12.8 months and 13.1 months, respectively.

Population: Safety population participants who achieved an overall response (best response of PR or better)

Duration of response (DOR) is defined as the time from first evidence of PR or better to disease progression (PD) or death due to any cause per the IMWG-URC criteria. PD: * Increase of 25% from lowest response value in any of the following: * Serum M-component (absolute increase ≥ 0.5 g/dL) and/or * Urine M-component (absolute increase ≥ 200 mg/24 hours) * In patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase \>10 mg/dL) * Definite development of new or increase in size of existing bone lesions or soft tissue plasmacytomas * Development of hypercalcemia attributed solely to the plasma cell proliferative disorder. DOR was analyzed using the Kaplan-Meier method; Participants with no documented progression or death were censored at the date of their last disease assessment. DOR was determined based on both investigator and independent review committee response assessments.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=44 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Duration of Overall Response (DOR) Independent Review Committee Assessment	12.2 months Interval 7.4 to Could not be estimated due to the low number of events at the analysis cut-off date
Duration of Overall Response (DOR) Investigator Assessment	9.7 months Interval 7.4 to Could not be estimated due to the low number of events at the analysis cut-off date

SECONDARY outcome

Population: Safety population participants who achieved a best overall response of minimal response or better.

Duration of clinical benefit (DCB) is defined as the time from first evidence of MR or better to disease progression or death due to any cause based on the (IMWG-URC criteria. DCB was estimated using the Kaplan-Meier method; participants with no disease progression or death at the analysis cut-off date were censored at their last disease assessment date. Duration of clinical benefit was determined based on both investigator and independent review committee response assessments.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=59 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Duration of Clinical Benefit (DCB) Independent Review Committee Assessment	8.3 months Interval 7.3 to 15.1
Duration of Clinical Benefit (DCB) Investigator Assessment	8.6 months Interval 7.4 to 15.1

SECONDARY outcome

Population: Safety population

Progression-free survival (PFS) is defined as the time from first dose of any study treatment to the earlier of disease progression or death due to any cause according to the IMWG-URC criteria. PFS was analyzed using the Kaplan-Meier method; participants with no disease progression or death at the time of the data cut-off date were censored at the date of their last disease assessment; participants who started new anti-cancer therapy before disease progression or death were censored at their last disease assessment prior to starting new anti-cancer therapy. Progression-free survival was determined based on both investigator and independent review committee response assessments.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=123 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Progression-free Survival (PFS) Independent Review Committee Assessment	5.6 months Interval 4.6 to 6.5
Progression-free Survival (PFS) Investigator Assessment	5.5 months Interval 4.6 to 6.5

SECONDARY outcome

Timeframe: From first dose until the data cut-off date of 15 March 2019; median time on follow-up for survival was 15.3 months.

Population: Safety population

Overall survival (OS) is defined as the time from the first dose of any study treatment to the date of death due to any cause. Overall survival was analyzed using the Kaplan-Meier method; participants who were alive or lost to follow-up as of the data analysis cut-off date were censored at their date of last contact (last known to be alive).

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=123 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Overall Survival (OS)	15.2 months Interval 11.5 to Could not be estimated due to the low number of events at the time of the analysis.

SECONDARY outcome

Population: Safety population participants who achieved an overall response (best response of PR or better)

Time to response (TTR) is the time from the first dose of any study treatment to the first confirmed response (PR or better) based on both investigator and independent review committee response assessments.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=44 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Time to Response (TTR) Independent Review Committee Assessment	1.0 months Interval 1.0 to 11.0
Time to Response (TTR) Investigator Assessment	1.0 months Interval 1.0 to 11.0

SECONDARY outcome

Timeframe: Cycles 1 and 2, day 1 at predose, 5 minutes after the start of carfilzomib infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of infusion.

Population: Pharmacokinetic (PK) analyses were conducted on a subset of participants at selected sites. The PK analysis population included participants who received at least 1 dose of carfilzomib and had adequate data for the noncompartmental estimation of PK parameters. Results are reported for participants with available data at each time point.

Cmax is the maximum observed plasma concentration over the concentration-time profile of carfilzomib.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=24 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Cycle 1 Day 1 (20 mg/m²)	744 ng/mL Standard Deviation 326
Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Cycle 2 Day 1 (27 mg/m²)	1210 ng/mL Standard Deviation 678

SECONDARY outcome

Tmax of carfilzomib is the time at which maximum observed plasma concentrations of carfilzomib were observed.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=24 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Time to Maximum Plasma Concentration (Tmax) of Carfilzomib Cycle 1 Day 1 (20 mg/m²)	0.50 hours Interval 0.083 to 0.63
Time to Maximum Plasma Concentration (Tmax) of Carfilzomib Cycle 2 Day 1 (27 mg/m²)	0.50 hours Interval 0.083 to 0.6

SECONDARY outcome

AUClast of carfilzomib is the total area under the concentration-time curve beginning from time 0 to the time of the last measurable concentration of carfilzomib.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=24 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Area Under the Plasma Concentration Curve From Time 0 to the Last Measurable Concentration (AUClast) for Carfilzomib Cycle 1 Day 1 (20 mg/m²)	254 hr*ng/mL Standard Deviation 102
Area Under the Plasma Concentration Curve From Time 0 to the Last Measurable Concentration (AUClast) for Carfilzomib Cycle 2 Day 1 (27 mg/m²)	401 hr*ng/mL Standard Deviation 173

SECONDARY outcome

Population: Pharmacokinetic analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination (R²; goodness of fit) \< 0.8 or percent extrapolated AUC \> 20% were excluded from the analysis.

AUC0-inf of carfilzomib is the total area under the concentration-time curve beginning from time 0 extrapolated to infinity following carfilzomib dosing.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=23 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinity (AUC0-inf) for Carfilzomib Cycle 1 Day 1 (20 mg/m²)	256 hr*ng/mL Standard Deviation 104
Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinity (AUC0-inf) for Carfilzomib Cycle 2 Day 1 (27 mg/m²)	401 hr*ng/mL Standard Deviation 173

SECONDARY outcome

The terminal elimination half-life is the time required for plasma concentrations to fall by 50% in the terminal phase of the concentration-time profile.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=23 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Terminal Elimination Half-Life (T½) for Carfilzomib Cycle 1 Day 1 (20 mg/m²)	0.651 hours Standard Deviation 0.259
Terminal Elimination Half-Life (T½) for Carfilzomib Cycle 2 Day 1 (27 mg/m²)	0.792 hours Standard Deviation 0.281

SECONDARY outcome

Systemic clearance is a measure of the ability of the body to eliminate drug, expressed in units of volume per time.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=23 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Systemic Clearance (CL) of Carfilzomib After Intravenous Infusion Cycle 1 Day 1 (20 mg/m²)	157 L/hr Standard Deviation 61.4
Systemic Clearance (CL) of Carfilzomib After Intravenous Infusion Cycle 2 Day 1 (27 mg/m²)	153 L/hr Standard Deviation 112

SECONDARY outcome

Volume of distribution is a pharmacokinetic parameter relating the amount of drug in the body to the concentration of drug in plasma.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=23 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Volume of Distribution (Varea) of Carfilzomib Cycle 1 Day 1 (20 mg/m²)	148 Liters Standard Deviation 88.7
Volume of Distribution (Varea) of Carfilzomib Cycle 2 Day 1 (27 mg/m²)	164 Liters Standard Deviation 102

SECONDARY outcome

Population: PK analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination \< 0.8, percent extrapolated AUC \> 20%, or negative values for Vss were excluded from the analysis.

Volume of distribution at steady-state is a pharmacokinetic parameter that relates the amount of drug in the body at steady-state to the concentration of drug in the plasma.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=22 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Volume of Distribution at Steady State (Vss) for Carfilzomib Cycle 1 Day 1 (20 mg/m²)	35.0 liters Standard Deviation 20.2
Volume of Distribution at Steady State (Vss) for Carfilzomib Cycle 2 Day 1 (27 mg/m²)	27.2 liters Standard Deviation 17.4

SECONDARY outcome

Population: PK analyses were conducted on a subset of participants at selected sites. Results are reported for the participants in PK analysis population with available data at each time point. PK profiles with a coefficient of determination \< 0.8, percent extrapolated AUC \> 20%, or negative values for MRT were excluded from the analysis.

MRTlast is the mean residence time observed from time 0 until the time of the last quantifiable concentration.

Outcome measures

Outcome measures
Measure	Carfilzomib With Dexamethasone n=23 Participants Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Mean Residence Time Observed From Time Zero to the Last Quantifiable Concentration (MRTlast) for Carfilzomib Cycle 1 Day 1 (20 mg/m²)	0.225 hours Standard Deviation 0.0856
Mean Residence Time Observed From Time Zero to the Last Quantifiable Concentration (MRTlast) for Carfilzomib Cycle 2 Day 1 (27 mg/m²)	0.196 hours Standard Deviation 0.0975

Adverse Events

Carfilzomib With Dexamethasone

Serious events: 68 serious events

Other events: 123 other events

Deaths: 91 deaths

Serious adverse events

Serious adverse events
Measure	Carfilzomib With Dexamethasone n=123 participants at risk Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Blood and lymphatic system disorders Thrombocytopenia	1.6% 2/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Cardiac disorders Cardiac amyloidosis	1.6% 2/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure acute	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Cardiac disorders Supraventricular tachycardia	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Eye disorders Cataract	6.5% 8/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
General disorders Disease progression	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
General disorders Infusion site extravasation	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
General disorders Pain	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
General disorders Pyrexia	3.3% 4/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatic function abnormal	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Bronchiolitis	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Bronchitis	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Device related infection	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Escherichia sepsis	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Influenza	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Localised infection	1.6% 2/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Otitis media	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Periodontitis	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Pneumonia	21.1% 26/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Respiratory tract infection	3.3% 4/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Soft tissue infection	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	1.6% 2/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Spinal compression fracture	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Platelet count decreased	2.4% 3/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	1.6% 2/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Bone pain	1.6% 2/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pathological fracture	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	3.3% 4/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Nervous system disorders Myelopathy	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Renal and urinary disorders Acute kidney injury	3.3% 4/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Renal and urinary disorders Chronic kidney disease	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Renal and urinary disorders Dysuria	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Asthma	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Organising pneumonia	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Vascular disorders Deep vein thrombosis	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Vascular disorders Hypertension	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Vascular disorders Hypotension	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Pancreatitis acute	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Nervous system disorders Cerebral ischaemia	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Nervous system disorders Nerve compression	0.81% 1/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.

Other adverse events

Other adverse events
Measure	Carfilzomib With Dexamethasone n=123 participants at risk Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23. Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.
Blood and lymphatic system disorders Anaemia	61.8% 76/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukocytosis	8.9% 11/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	5.7% 7/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Eye disorders Vision blurred	5.7% 7/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	6.5% 8/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	13.8% 17/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	17.1% 21/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	5.7% 7/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	6.5% 8/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
General disorders Oedema peripheral	9.8% 12/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
General disorders Peripheral swelling	7.3% 9/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
General disorders Pyrexia	17.9% 22/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatic function abnormal	5.7% 7/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Bronchitis	9.8% 12/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Influenza	8.1% 10/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	6.5% 8/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Pneumonia	22.8% 28/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Respiratory tract infection	5.7% 7/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	48.8% 60/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	11.4% 14/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	9.8% 12/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Bilirubin conjugated increased	7.3% 9/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood albumin decreased	8.1% 10/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	13.8% 17/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood creatinine increased	18.7% 23/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood glucose increased	13.8% 17/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood lactate dehydrogenase increased	16.3% 20/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood phosphorus increased	8.1% 10/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood potassium decreased	9.8% 12/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood pressure increased	14.6% 18/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood urea increased	12.2% 15/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood uric acid increased	14.6% 18/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Gamma-glutamyltransferase increased	5.7% 7/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Lymphocyte count decreased	27.6% 34/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Lymphocyte percentage decreased	9.8% 12/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Mean cell volume increased	6.5% 8/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	30.1% 37/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Neutrophil count increased	16.3% 20/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Neutrophil percentage increased	12.2% 15/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Platelet count decreased	48.8% 60/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Prealbumin decreased	7.3% 9/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations White blood cell count decreased	39.0% 48/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations White blood cell count increased	13.8% 17/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	11.4% 14/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	13.8% 17/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	5.7% 7/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperuricaemia	17.1% 21/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	16.3% 20/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	16.3% 20/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	35.0% 43/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	10.6% 13/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypophosphataemia	7.3% 9/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoproteinaemia	8.1% 10/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	7.3% 9/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Nervous system disorders Neuropathy peripheral	9.8% 12/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	18.7% 23/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	21.1% 26/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Productive cough	9.8% 12/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Vascular disorders Hypertension	38.2% 47/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	5.7% 7/123 • All-cause mortality is reported from the date enrolled until the end of study, median (minimum, maximum) time on study was 14.32 (0.066, 47.28) months. Adverse events are reported from the first dose of any study treatment up to 30 days after the end of study treatment, or initiation of new antimyeloma therapy, whichever occurred first; median (minimum, maximum) duration of treatment was 20.3 (0.3, 203) weeks. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER