Trial Outcomes & Findings for Clinical Study With Blinatumomab in Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) (NCT NCT01466179)

Last Updated: 2017-08-18

Results Overview

Hematological assessments were performed from bone marrow biopsy samples. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Hematological remissions were defined by the following criteria: Complete Remission (CR): * bone marrow blasts ≤ 5% * no evidence of disease * full recovery of peripheral blood counts: * platelets \> 100,000/μL, and * absolute neutrophil count (ANC) \> 1,000/μL Complete Remission With Partial Hematological Recovery (CRh\*): * bone marrow blasts ≤ 5% * no evidence of disease * partial recovery of peripheral blood counts: * platelets \> 50,000/μL, and * ANC \> 500/μL.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

225 participants

Primary outcome timeframe

Within the first 2 cycles of treatment, 12 weeks

Results posted on

2017-08-18

Participant Flow

This study was open to adult patients with relapsed / refractory B-precursor acute lymphoblastic leukemia (ALL). The study protocol originally used a Simon 2-stage design and was subsequently expanded to include a third stage. Protocol amendment 4 added an additional cohort of participants for central nervous system evaluations.

Two hundred twenty-five participants enrolled in the study overall. Results below include data for 189 participants enrolled in the first 3 stages of the study (the primary analysis set). An additional 36 participants enrolled in the Additional Evaluation Cohort are not reported here as the study is ongoing and data collection has not completed.

Participant milestones

Participant milestones
Measure	Blinatumomab Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.
Overall Study STARTED	189
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	179

Reasons for withdrawal

Reasons for withdrawal
Measure	Blinatumomab Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.
Overall Study Ongoing in core study	2
Overall Study Physician Decision	46
Overall Study Progressive disease	43
Overall Study Adverse Event	32
Overall Study Disease relapse	23
Overall Study Lack of Efficacy	14
Overall Study Death	7
Overall Study Withdrawal by Subject	7
Overall Study Protocol Violation	2
Overall Study Other	3

Baseline Characteristics

Clinical Study With Blinatumomab in Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Blinatumomab n=189 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.
Age, Continuous	39.0 years n=5 Participants
Age, Customized 18 to < 35 years	90 participants n=5 Participants
Age, Customized 35 to < 55 years	46 participants n=5 Participants
Age, Customized 55 to < 65 years	28 participants n=5 Participants
Age, Customized ≥ 65 years	25 participants n=5 Participants
Sex: Female, Male Female	70 Participants n=5 Participants
Sex: Female, Male Male	119 Participants n=5 Participants
Race/Ethnicity, Customized White	145 participants n=5 Participants
Race/Ethnicity, Customized Asian	6 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	7 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska native	1 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 participants n=5 Participants
Race/Ethnicity, Customized Other	9 participants n=5 Participants
Race/Ethnicity, Customized Not recorded	20 participants n=5 Participants
Disease stage entry criteria met Primary refractory	16 participants n=5 Participants
Disease stage entry criteria met Relapse ≤ 12 months of allogeneic HSCT	39 participants n=5 Participants
Disease stage entry criteria met Entering first salvage; first remission ≤ 12 mo	23 participants n=5 Participants
Disease stage entry criteria met Entering second or greater salvage therapies	108 participants n=5 Participants
Disease stage entry criteria met No criteria met	3 participants n=5 Participants
Number of prior relapses 0	16 participants n=5 Participants
Number of prior relapses 1	107 participants n=5 Participants
Number of prior relapses 2	46 participants n=5 Participants
Number of prior relapses >2	20 participants n=5 Participants
Prior allogeneic HSCT and prior relapses Prior allogeneic HSCT	64 participants n=5 Participants
Prior allogeneic HSCT and prior relapses No prior alloHSCT, no prior relapse	16 participants n=5 Participants
Prior allogeneic HSCT and prior relapses No prior alloHSCT, 1 prior relapse	84 participants n=5 Participants
Prior allogeneic HSCT and prior relapses No prior alloHSCT, 2 prior relapses	22 participants n=5 Participants
Prior allogeneic HSCT and prior relapses No prior alloHSCT, > 2 prior relapses	3 participants n=5 Participants
Number of prior salvage therapies No prior salvage therapy	38 participants n=5 Participants
Number of prior salvage therapies 1 prior salvage therapy	77 participants n=5 Participants
Number of prior salvage therapies 2 prior salvage therapies	42 participants n=5 Participants
Number of prior salvage therapies > 2 prior salvage therapies	32 participants n=5 Participants
Time since initial diagnosis	16.59 months n=5 Participants
Time since last relapse	1.38 months n=5 Participants
Baseline bone marrow blast category < 10%	1 participants n=5 Participants
Baseline bone marrow blast category 10% - < 50%	43 participants n=5 Participants
Baseline bone marrow blast category ≥ 50%	145 participants n=5 Participants

PRIMARY outcome

Timeframe: Within the first 2 cycles of treatment, 12 weeks

Population: The Primary Analysis Set (PAS), defined as participants from the first 3 stages of the study who received any infusion of blinatumomab.

Outcome measures

Outcome measures
Measure	Blinatumomab n=189 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment	42.9 percentage of participants Interval 35.7 to 50.2	—	—

SECONDARY outcome

Timeframe: Up to the data cut-off date of 10 October 2013; median observation time was 8.0 months.

Population: Participants who reached complete remission or complete remission with partial hematological recovery during the core study.

Time to hematological relapse was measured for participants in remission during the core study (the time from the first infusion through 30 days after the last infusion), from the time the participant first achieved remission until first documented relapse or death due to disease progression. Participants without documented relapse (hematological or extramedullary) and who did not die were censored at the time of their last bone marrow assessment or their last survival follow-up visit confirming remission. Participants who died without having reported hematological relapse or without showing any clinical sign of disease progression were censored on their date of death. Hematological relapse is defined as: * proportion of blasts in bone marrow \> 5% after documented CR/CRh\* or * blasts in peripheral blood after documented CR/CRh\*. Time to hematological relapse was analyzed by Kaplan-Meier methods and the median observation time was calculated by the reverse Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Blinatumomab n=82 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Time to Hematological Relapse (Duration of Response)	6.7 months Interval 5.1 to Not estimable due to the number of events during the observation period.	—	—

SECONDARY outcome

Timeframe: Up to the data cut-off date of 10 October 2013. Maximum duration on study was 17.8 months.

Population: Participants who reached complete remission or complete remission with partial hematological recovery during the first 2 cycles of treatment.

Participants who were eligible for allogeneic HSCT were those who achieved remission (complete response or complete response with partial recovery of peripheral blood counts) after 2 cycles of blinatumomab treatment, and no further anti-leukemic medication was given before HSCT.

Outcome measures

Outcome measures
Measure	Blinatumomab n=81 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) During Blinatumomab Induced Remission	39.5 percentage of participants Interval 28.8 to 51.0	—	—

SECONDARY outcome

Timeframe: Within the first 2 cycles of treatment, 12 weeks

Population: Primary analysis set

Complete Remission was defined by the following criteria: * bone marrow blasts ≤ 5% * no evidence of disease * full recovery of peripheral blood counts: * platelets \> 100,000/μL, and * absolute neutrophil count (ANC) \> 1,000/μL

Outcome measures

Outcome measures
Measure	Blinatumomab n=189 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Percentage of Participants With a Best Response of Complete Remission Within 2 Cycles of Treatment	33.3 percentage of participants Interval 26.7 to 40.5	—	—

SECONDARY outcome

Timeframe: Within the first 2 cycles of treatment, 12 weeks

Population: Primary analysis set

Complete Remission With Partial Hematological Recovery was defined by the following criteria: * bone marrow blasts ≤ 5% * no evidence of disease * partial recovery of peripheral blood counts: * platelets \> 50,000/μL, and * ANC \> 500/μL.

Outcome measures

Outcome measures
Measure	Blinatumomab n=189 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Percentage of Participants With a Best Response of Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment	9.5 percentage of participants Interval 5.7 to 14.6	—	—

SECONDARY outcome

Timeframe: Within the first 2 cycles of treatment, 12 weeks

Population: Primary analysis set

Partial Remission is defined as bone marrow blasts 6% to 25% with at least a 50% reduction from baseline.

Outcome measures

Outcome measures
Measure	Blinatumomab n=189 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Percentage of Participants With a Best Response of Partial Remission Within 2 Cycles of Treatment	2.6 percentage of participants Interval 0.9 to 6.1	—	—

SECONDARY outcome

Timeframe: Up to the data cut-off date of 10 October 2013; median observation time was 8.9 months.

Population: Participants who reached complete remission or complete remission with partial hematological recovery during the core study

Relapse-free survival was assessed for participants who achieved a complete remission or complete remission with partial hematological recovery during the core study and was measured from the time the participant first achieved remission until first documented relapse or death due to any cause. Participants without a documented relapse (hematological or extramedullary) or who did not die were censored at the time of their last bone marrow assessment or their last survival follow-up visit confirming remission. Relapse free survival was estimated using Kaplan-Meier methods and the median observation time was calculated by the reverse Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Blinatumomab n=82 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Relapse-free Survival	5.9 months Interval 4.8 to 8.3	—	—

SECONDARY outcome

Timeframe: Up to the data cut-off date of 10 October 2013; median observation time was 9.8 months.

Population: Primary analysis set

Event-free survival was calculated from the start date of blinatumomab infusion until the date of bone marrow aspiration at which hematological relapse was first detected, or the date of diagnosis on which the hematological or extramedullary relapse was documented or the date of start of any new therapy for ALL (excluding HSCT), or the date of death, whichever was earlier. Participants who did not achieve complete remission or complete remission with partial hematological recovery during the core study were evaluated as having an event on Day 1. Participants in remission who did not experience hematological relapse, did not receive a new therapy for ALL (excluding HSCT), and did not die were censored on the date of the last available bone marrow aspiration or on the last date of survival follow-up visit, whichever was later. Event free survival was estimated using Kaplan-Meier methods and the median observation time was calculated by the reverse Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Blinatumomab n=189 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Event-free Survival	0.0 months Interval 0.0 to 1.0	—	—

SECONDARY outcome

Timeframe: Up to the data cut-off date of 10 October 2013; median observation time was 9.8 months.

Population: Primary analysis set

Overall survival was measured for all participants from the time the participant received the first treatment of blinatumomab until death due to any cause or the date of the last follow-up. Participants who did not die were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive. Overall survival was estimated using Kaplan-Meier methods. The median follow-up time with respect to overall survival was calculated by the reverse Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Blinatumomab n=189 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Overall Survival	6.1 months Interval 4.2 to 7.5	—	—

SECONDARY outcome

Timeframe: From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days.

Population: Full analysis set (FAS), defined as all patients who received any infusion of blinatumomab.

Adverse events (AEs) were evaluated for severity according to the the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4, as follows: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death. The investigator used medical judgment to determine if there was a causal relationship (ie, related, unrelated) between an adverse event and blinatumomab. An AE was considered "serious" if it resulted in death, was life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant incapacity or substantial disruption to conduct normal life functions, is a congenital anomaly or birth defect or is a medically important condition. Progressive disease was not an adverse event, per the protocol, unless it was more severe than expected for the patient. Therefore, many deaths due to progressive disease were not counted as adverse events.

Outcome measures

Outcome measures
Measure	Blinatumomab n=189 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Number of Participants With Treatment-emergent Adverse Events Any adverse event (AE)	188 participants	—	—
Number of Participants With Treatment-emergent Adverse Events Adverse events of at least CTC grade 3	155 participants	—	—
Number of Participants With Treatment-emergent Adverse Events Treatment-related adverse events	166 participants	—	—
Number of Participants With Treatment-emergent Adverse Events Related adverse events of at least CTC grade 3	105 participants	—	—
Number of Participants With Treatment-emergent Adverse Events Serious adverse events	121 participants	—	—
Number of Participants With Treatment-emergent Adverse Events Serious adverse events of at least CTC grade 3	105 participants	—	—
Number of Participants With Treatment-emergent Adverse Events Related serious adverse events	69 participants	—	—
Number of Participants With Treatment-emergent Adverse Events AEs leading to interruption of blinatumomab	63 participants	—	—
Number of Participants With Treatment-emergent Adverse Events AEs leading to discontinuation of blinatumomab	34 participants	—	—
Number of Participants With Treatment-emergent Adverse Events Related AE leading to treatment discontinuation	18 participants	—	—
Number of Participants With Treatment-emergent Adverse Events AEs leading to death	28 participants	—	—
Number of Participants With Treatment-emergent Adverse Events Related AEs leading to death	3 participants	—	—

SECONDARY outcome

Timeframe: From the date of allogeneic HSCT until the data cut-off date of 10 October 2013; median observation time was 7.4 months.

Population: Participants who received an allogeneic HSCT while in remission induced by blinatumomab treatment.

The analysis of 100-day mortality after allogeneic HSCT was assessed for all participants who received an allogeneic HSCT while in remission (CR/CRh\*) following treatment with blinatumomab. 100-day mortality after allogeneic HSCT was calculated relative to the date of allogeneic HSCT. Patients alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive. The 100-day mortality rate after allogeneic HSCT was defined as the percentage of patients having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	Blinatumomab n=32 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant	11.3 percentage of participants Interval 0.0 to 23.4	—	—

SECONDARY outcome

Timeframe: Samples were taken before treatment start and on Days 3, 8, 10, 15, 22, and 29 after infusion start during Cycles 1 and 2.

Population: Pharmacokinetic Data Set (PKS) defined as all patients who received any infusion of blinatumomab and had at least one PK sample collected unless significant protocol deviations affected the data analysis or if key dosing, dosing interruption or sampling information was missing.

The steady state concentration of blinatumomab was summarized as the observed concentrations collected at least 10 hours after the start of the IV infusion or dose step for cycle 1 and cycle 2, respectively. Serum concentrations of blinatumomab were measured using a validated bioassay. The lower limit of quantitation (LLOQ) = 50.0 pg/mL.

Outcome measures

Outcome measures
Measure	Blinatumomab n=132 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day n=160 Participants Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day n=88 Participants Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Serum Blinatumomab Concentration at Steady State	211 pg/mL Standard Deviation 258	621 pg/mL Standard Deviation 502	731 pg/mL Standard Deviation 444

SECONDARY outcome

Timeframe: Serum samples were collected on Days 1 and 8 at 2 hours and 6 hours after treatment start, and on Day 2 (24 hours) and Day 3 (48 hours) of each treatment cycle and on Days 9 and 10 after dose step.

Population: Pharmacodynamic Data Set (PDS): All patients who received any infusion of blinatumomab and had at least one pharmacodynamic sample collected. N indicates the number of participants with available data at each time point.

The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN)-γ using enzyme-linked immunosorbent assays or cytometric bead assays. The limit of detection of the assay (LOD) was 20 pg/mL and the limit of quantification (LOQ) was 125 pg/mL. Data below LOD were set to 10 pg/mL while data \< LOQ and \> LOD were reported as measured. Serum IL-4 levels were below detection limit (\< 20 pg/mL) at all time points in all participants studied.

Outcome measures

Outcome measures
Measure	Blinatumomab n=189 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Serum Cytokine Peak Levels IFN-Ɣ: Cycle 1 Week 1 (N=184)	93.1 pg/mL Standard Deviation 409	—	—
Serum Cytokine Peak Levels IFN-Ɣ: Cycle 1 Week 2 (N=175)	27.4 pg/mL Standard Deviation 83.1	—	—
Serum Cytokine Peak Levels IFN-Ɣ: Cycle 2 Week 1 (N=95)	22.8 pg/mL Standard Deviation 45.8	—	—
Serum Cytokine Peak Levels IFN-Ɣ: Cycle 3 Week 1 (N=41)	21.6 pg/mL Standard Deviation 27.6	—	—
Serum Cytokine Peak Levels IL-10: Cycle 1 Week 1 (N=184)	589 pg/mL Standard Deviation 822	—	—
Serum Cytokine Peak Levels IL-10: Cycle 1 Week 2 (N=175)	95.7 pg/mL Standard Deviation 136	—	—
Serum Cytokine Peak Levels IL-10: Cycle 2 Week 1 (N=95)	397 pg/mL Standard Deviation 633	—	—
Serum Cytokine Peak Levels IL-10: Cycle 3 Week 1 (N=41)	428 pg/mL Standard Deviation 941	—	—
Serum Cytokine Peak Levels IL-2: Cycle 1 Week 1 (N=184)	24.7 pg/mL Standard Deviation 44.6	—	—
Serum Cytokine Peak Levels IL-2: Cycle 1 Week 2 (N=175)	10.8 pg/mL Standard Deviation 5.21	—	—
Serum Cytokine Peak Levels IL-2: Cycle 2 Week 1 (N=95)	11 pg/mL Standard Deviation 5.17	—	—
Serum Cytokine Peak Levels IL-2: Cycle 3 Week 1 (N=41)	10.3 pg/mL Standard Deviation 2.03	—	—
Serum Cytokine Peak Levels IL-6: Cycle 1 Week 1 (N=184)	826 pg/mL Standard Deviation 2390	—	—
Serum Cytokine Peak Levels IL-6: Cycle 1 Week 2 (N=175)	234 pg/mL Standard Deviation 681	—	—
Serum Cytokine Peak Levels IL-6: Cycle 2 Week 1 (N=95)	315 pg/mL Standard Deviation 952	—	—
Serum Cytokine Peak Levels IL-6: Cycle 3 Week 1 (N=41)	69.2 pg/mL Standard Deviation 114	—	—
Serum Cytokine Peak Levels TNF-α: Cycle 1 Week 1 (N=184)	30 pg/mL Standard Deviation 125	—	—
Serum Cytokine Peak Levels TNF-α: Cycle 1 Week 2 (N=175)	10.3 pg/mL Standard Deviation 3.33	—	—
Serum Cytokine Peak Levels TNF-α: Cycle 2 Week 1 (N=95)	12.1 pg/mL Standard Deviation 15	—	—
Serum Cytokine Peak Levels TNF-α: Cycle 3 Week 1 (N=41)	12 pg/mL Standard Deviation 7.79	—	—

SECONDARY outcome

Timeframe: Within the first 2 cycles of treatment, 12 weeks

Population: Primary analysis set

Blast Free Hypoplastic or Aplastic Bone Marrow was defined as: * bone marrow blasts ≤ 5% * no evidence of disease * insufficient recovery of peripheral counts: platelets ≤ 50,000/μL and/or absolute neutrophil count (ANC) ≤ 500/μL

Outcome measures

Outcome measures
Measure	Blinatumomab n=189 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Percentage of Participants With a Best Response of Blast Free Hypoplastic or Aplastic Bone Marrow Within 2 Cycles of Treatment	9.0 percentage of participants Interval 5.3 to 14.0	—	—

SECONDARY outcome

Timeframe: From the first dose of blinatumomab until 30 days after the end of the last infusion during the core study, or until the data cut-off date of 10 October 2013; a maximum of 7.5 months.

Population: Primary analysis set

Complete Remission (CR): * bone marrow blasts ≤ 5% * no evidence of disease * full recovery of peripheral blood counts: * platelets \> 100,000/μL, and * absolute neutrophil count (ANC) \> 1,000/μL Complete Remission With Partial Hematological Recovery (CRh\*): * bone marrow blasts ≤ 5% * no evidence of disease * partial recovery of peripheral blood counts: * platelets \> 50,000/μL, and * ANC \> 500/μL Blast Free Hypoplastic or Aplastic Bone Marrow: * bone marrow blasts ≤ 5% * no evidence of disease * insufficient recovery of peripheral counts: platelets ≤ 50,000/μL and/or ANC ≤ 500/μL Partial Remission: • bone marrow blasts 6% to 25% with at least a 50% reduction from Baseline.

Outcome measures

Outcome measures
Measure	Blinatumomab n=189 Participants Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.	Cycle 1: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 1.	Cycle 2: Blinatumomab 28 μg/Day Participants receiving 28 μg/day blinatumomab by continuous intravenous (CIV) infusion during Cycle 2.
Best Response During the Core Study Remission (CR/CRh*)	43.4 percentage of participants Interval 36.2 to 50.8	—	—
Best Response During the Core Study Complete Remission	35.4 percentage of participants Interval 28.6 to 42.7	—	—
Best Response During the Core Study Complete remission with only partial hematological	7.9 percentage of participants Interval 4.5 to 12.8	—	—
Best Response During the Core Study Blast free hypoplastic or aplastic bone marrow	9.0 percentage of participants Interval 5.3 to 14.0	—	—
Best Response During the Core Study Partial remission	2.6 percentage of participants Interval 0.9 to 6.1	—	—

Adverse Events

Blinatumomab

Serious events: 121 serious events

Other events: 186 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Blinatumomab n=189 participants at risk Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The the initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.
Blood and lymphatic system disorders Anaemia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Febrile neutropenia	8.5% 16/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Leukocytosis	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Lymphopenia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Neutropenia	3.7% 7/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Pancytopenia	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Atrial fibrillation	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Bradycardia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiac failure	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiac failure congestive	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Sinus bradycardia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Supraventricular tachycardia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Ventricular fibrillation	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Congenital, familial and genetic disorders Aplasia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Eye disorders Diplopia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Colitis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Enteritis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Pancreatitis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Asthenia	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Chest pain	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Device occlusion	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Disease progression	1.6% 3/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Hypothermia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Medical device complication	1.6% 3/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Mucosal inflammation	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Multi-organ failure	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Oedema peripheral	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	5.8% 11/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Immune system disorders Cytokine release syndrome	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Immune system disorders Hypersensitivity	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Abdominal infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Aspergillus infection	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations BK virus infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Bacterial sepsis	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Bronchopneumonia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Bronchopulmonary aspergillosis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Candida infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Cellulitis	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Cholecystitis infective	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Device related infection	3.7% 7/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Enterobacter infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Enterococcal bacteraemia	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Enterococcal infection	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Enterococcal sepsis	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Epididymal infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Erysipelas	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Escherichia sepsis	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Fungal infection	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Fusarium infection	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Gastrointestinal infection	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Herpes zoster	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Infection	2.1% 4/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Kidney infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Klebsiella infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Leuconostoc infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Lower respiratory tract infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Lung infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Neutropenic sepsis	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pathogen resistance	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pilonidal cyst	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pneumonia	4.8% 9/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pneumonia fungal	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pneumonia klebsiella	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pneumonia respiratory syncytial viral	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pseudomonal bacteraemia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pseudomonas infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pulmonary sepsis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Rhinitis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Rhinovirus infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Sepsis	4.8% 9/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Septic shock	1.6% 3/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Sinusitis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Sinusitis fungal	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Staphylococcal bacteraemia	2.1% 4/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Staphylococcal infection	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Staphylococcal sepsis	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Streptococcal sepsis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary tract infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urosepsis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Viral haemorrhagic cystitis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Viral infection	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Accidental overdose	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Femoral neck fracture	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Hip fracture	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Overdose	2.6% 5/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Post lumbar puncture syndrome	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Subdural haematoma	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Toxicity to various agents	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Alanine aminotransferase increased	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Aspartate aminotransferase increased	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Blood alkaline phosphatase increased	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Blood bilirubin increased	1.6% 3/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Blood creatinine increased	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Blood lactate dehydrogenase increased	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations C-reactive protein increased	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Neutrophil count decreased	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Platelet count decreased	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations White blood cell count decreased	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Fluid overload	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyperglycaemia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypokalaemia	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Tumour lysis syndrome	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthritis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Bone pain	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Fistula	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Muscular weakness	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Myopathy	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Pain in extremity	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute leukaemia	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute lymphocytic leukaemia	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B precursor type acute leukaemia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chloroma	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Aphasia	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Ataxia	1.6% 3/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Cerebral haemorrhage	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Cognitive disorder	1.6% 3/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Convulsion	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dizziness	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dysaesthesia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dysarthria	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Encephalopathy	2.6% 5/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	2.1% 4/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Hemiparesis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Nervous system disorder	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Neurological symptom	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Neurotoxicity	1.6% 3/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Paraesthesia	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Poor quality sleep	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Tremor	2.6% 5/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Trigeminal nerve disorder	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Agitation	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Confusional state	2.6% 5/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Delirium febrile	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Mental status changes	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Restlessness	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Bladder perforation	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal failure	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal failure acute	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Reproductive system and breast disorders Scrotal oedema	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.6% 3/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Erythema multiforme	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Rash vesicular	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Skin lesion	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Surgical and medical procedures Catheter placement	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Surgical and medical procedures Central venous catheter removal	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Surgical and medical procedures Resuscitation	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Capillary leak syndrome	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Embolism	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Femoral artery occlusion	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	1.1% 2/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypovolaemic shock	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Subclavian vein thrombosis	0.53% 1/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Other adverse events
Measure	Blinatumomab n=189 participants at risk Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The the initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.
Blood and lymphatic system disorders Anaemia	19.6% 37/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Febrile neutropenia	20.1% 38/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Leukopenia	10.1% 19/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Neutropenia	13.8% 26/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Thrombocytopenia	11.1% 21/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Sinus tachycardia	5.8% 11/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Tachycardia	5.8% 11/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Eye disorders Vision blurred	6.3% 12/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal distension	5.8% 11/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain	16.4% 31/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain upper	5.3% 10/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Constipation	20.6% 39/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	18.0% 34/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	24.3% 46/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	13.2% 25/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Asthenia	9.0% 17/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Chest pain	10.1% 19/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Chills	15.3% 29/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	14.8% 28/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Oedema	5.8% 11/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Oedema peripheral	25.9% 49/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pain	7.4% 14/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	56.1% 106/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Immune system disorders Cytokine release syndrome	11.6% 22/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Upper respiratory tract infection	5.3% 10/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Alanine aminotransferase increased	12.2% 23/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Aspartate aminotransferase increased	10.6% 20/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Blood bilirubin increased	6.3% 12/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Immunoglobulins decreased	9.0% 17/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Weight increased	8.5% 16/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Decreased appetite	10.1% 19/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyperglycaemia	12.2% 23/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypokalaemia	23.3% 44/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypomagnesaemia	13.2% 25/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypophosphataemia	6.9% 13/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	9.5% 18/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	13.2% 25/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Bone pain	9.5% 18/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Muscle spasms	5.3% 10/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Muscular weakness	7.4% 14/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Myalgia	9.0% 17/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Pain in extremity	10.6% 20/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dizziness	13.2% 25/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	33.3% 63/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Tremor	17.5% 33/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Anxiety	7.4% 14/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Insomnia	15.3% 29/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Cough	18.5% 35/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.5% 16/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.8% 11/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Petechiae	5.8% 11/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Rash	11.6% 22/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	6.3% 12/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	11.1% 21/189 • From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

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.
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Restriction type: OTHER