Trial Outcomes & Findings for Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Multiple Myeloma (NCT NCT01818752)

Last Updated: 2019-08-26

Results Overview

Progression-free survival was defined as the time from randomization to the earlier of documented disease progression or death due to any cause. PFS was analyzed using Kaplan-Meier methods. The duration of PFS was censored for participants with no baseline and/or post-baseline disease assessments, who started a new anti-cancer therapy before documentation of disease progression or death, death or disease progression after missed disease assessment of 100 consecutive days or longer, or who were alive without documentation of disease progression before the data cutoff date, including lost to follow-up prior to disease progression. Participants were evaluated for disease response and progression according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC), determined centrally using a validated computer algorithm in a blinded manner.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

955 participants

Primary outcome timeframe

From randomization until the data cut-off date of 15 July 2016; median follow-up time for PFS was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.

Results posted on

2019-08-26

Participant Flow

This study was conducted at 183 centers in Argentina, Australia, Austria, Belgium, Bulgaria, Canada, China, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Poland, Romania, Russia, Singapore, South Korea, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, and United States.

Eligible participants were randomized in a 1:1 ratio. Randomization was stratified by International Staging System (ISS) stage (stage 1 versus stages 2 or 3), choice of route of bortezomib administration (intravenous \[IV\] versus subcutaneous \[SC\]), region (North America, Europe, Asia Pacific, or other), and age (\< 75 years versus ≥ 75 years).

Participant milestones

Participant milestones
Measure	Bortezomib, Melphalan, Prednisone Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Carfilzomib, Melphalan, Prednisone Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Overall Study STARTED	477	478
Overall Study Received Treatment	470	474
Overall Study COMPLETED	290	280
Overall Study NOT COMPLETED	187	198

Reasons for withdrawal

Reasons for withdrawal
Measure	Bortezomib, Melphalan, Prednisone Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Carfilzomib, Melphalan, Prednisone Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Overall Study Adverse Event	64	74
Overall Study Death	14	18
Overall Study Non-compliance	16	20
Overall Study Withdrawal by Subject	15	14
Overall Study Physician Decision	9	8
Overall Study Disease Progression	54	48
Overall Study Other	7	8
Overall Study Continuing Treatment	1	4
Overall Study Randomized but not Dosed	7	4

Baseline Characteristics

Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bortezomib, Melphalan, Prednisone n=477 Participants Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Carfilzomib, Melphalan, Prednisone n=478 Participants Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Total n=955 Participants Total of all reporting groups
Age, Continuous	71.5 years STANDARD_DEVIATION 6.5 • n=5 Participants	72.0 years STANDARD_DEVIATION 5.7 • n=7 Participants	71.7 years STANDARD_DEVIATION 6.1 • n=5 Participants
Sex: Female, Male Female	238 Participants n=5 Participants	235 Participants n=7 Participants	473 Participants n=5 Participants
Sex: Female, Male Male	239 Participants n=5 Participants	243 Participants n=7 Participants	482 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	18 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	443 Participants n=5 Participants	427 Participants n=7 Participants	870 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	19 Participants n=5 Participants	33 Participants n=7 Participants	52 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Asian	121 participants n=5 Participants	123 participants n=7 Participants	244 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized White	339 participants n=5 Participants	329 participants n=7 Participants	668 participants n=5 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Multiple	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Not Reported	12 participants n=5 Participants	19 participants n=7 Participants	31 participants n=5 Participants
Stratification Factor: International Staging System (ISS) Stage Stage I	99 participants n=5 Participants	95 participants n=7 Participants	194 participants n=5 Participants
Stratification Factor: International Staging System (ISS) Stage Stage II or III	378 participants n=5 Participants	383 participants n=7 Participants	761 participants n=5 Participants
Stratification Factor: Route of Bortezomib Administration Intravenous	123 participants n=5 Participants	123 participants n=7 Participants	246 participants n=5 Participants
Stratification Factor: Route of Bortezomib Administration Subcutaneous	354 participants n=5 Participants	355 participants n=7 Participants	709 participants n=5 Participants
Stratification Factor: Region of Enrollment Asia Pacific	141 participants n=5 Participants	140 participants n=7 Participants	281 participants n=5 Participants
Stratification Factor: Region of Enrollment North America	12 participants n=5 Participants	8 participants n=7 Participants	20 participants n=5 Participants
Stratification Factor: Region of Enrollment Europe	317 participants n=5 Participants	320 participants n=7 Participants	637 participants n=5 Participants
Stratification Factor: Region of Enrollment Other	7 participants n=5 Participants	10 participants n=7 Participants	17 participants n=5 Participants
Stratification Factor: Age < 75 years	329 participants n=5 Participants	327 participants n=7 Participants	656 participants n=5 Participants
Stratification Factor: Age ≥ 75 years	148 participants n=5 Participants	151 participants n=7 Participants	299 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully active)	125 participants n=5 Participants	129 participants n=7 Participants	254 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restrictive but ambulatory)	250 participants n=5 Participants	260 participants n=7 Participants	510 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 (Ambulatory but unable to work)	101 participants n=5 Participants	89 participants n=7 Participants	190 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Missing	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until the data cut-off date of 15 July 2016; median follow-up time for PFS was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.

Population: The intent-to-treat population included all randomized participants.

Outcome measures

Outcome measures
Measure	Bortezomib, Melphalan, Prednisone n=477 Participants Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Carfilzomib, Melphalan, Prednisone n=478 Participants Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Progression-Free Survival (PFS)	22.1 months Interval 20.8 to 24.4	22.3 months Interval 20.9 to 26.7

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 15 July 2016; median follow-up time for OS was 22.2 and 22.5 months in the bortezomib and carfilzomib arms respectively.

Population: Intent-to-treat population

Overall survival (OS) was defined as the time from randomization to the date of death (whatever the cause). Participants who were alive or lost to follow-up as of the data analysis cut-off date were censored on the date the patient was last known to be alive. Median overall survival was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Bortezomib, Melphalan, Prednisone n=477 Participants Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Carfilzomib, Melphalan, Prednisone n=478 Participants Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Overall Survival (OS)	NA months Not estimable due to the low number of events	NA months Interval 31.5 to Not estimable due to the low number of events

SECONDARY outcome

Timeframe: Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.

Population: Intent-to-treat population

Disease response was evaluated according to the IMWG-URC using a validated computer algorithm. Overall response was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in BM biopsy; VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein \<100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline. PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to \< 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.

Outcome measures

Outcome measures
Measure	Bortezomib, Melphalan, Prednisone n=477 Participants Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Carfilzomib, Melphalan, Prednisone n=478 Participants Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Overall Response Rate	78.8 percentage of participants Interval 74.9 to 82.4	84.3 percentage of participants Interval 80.7 to 87.5

SECONDARY outcome

Population: Intent-to-treat population

Complete response rate was defined as the percentage of participants in each treatment group who achieved a sCR or CR per the IMWG-URC as their best response. sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in BM biopsy.

Outcome measures

Outcome measures
Measure	Bortezomib, Melphalan, Prednisone n=477 Participants Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Carfilzomib, Melphalan, Prednisone n=478 Participants Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Complete Response Rate	23.1 percentage of participants Interval 19.4 to 27.1	25.9 percentage of participants Interval 22.1 to 30.1

SECONDARY outcome

Timeframe: From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups.

Population: The safety population included all randomized participants who received at least 1 dose of any study treatment (i.e., carfilzomib, bortezomib, melphalan, or prednisone).

Neuropathy events were defined as Grade 2 or higher peripheral neuropathy as specified by peripheral neuropathy Standardised Medical Dictionary for Regulatory Activities (MedDRA) Query, narrow (scope) (SMQN) terms. Peripheral neuropathy was assessed by neurologic exam and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03: Grade 1: Asymptomatic; Grade 2: Moderate symptoms, limiting instrumental activities of daily living (ADL) Grade 3: Severe symptoms; limiting self-care ADL; Grade 4: Life-threatening consequences, urgent intervention indicated; Grade 5: Death.

Outcome measures

Outcome measures
Measure	Bortezomib, Melphalan, Prednisone n=470 Participants Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Carfilzomib, Melphalan, Prednisone n=474 Participants Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Percentage of Participants With ≥ Grade 2 Peripheral Neuropathy	35.1 percentage of participants Interval 30.8 to 39.6	2.5 percentage of participants Interval 1.3 to 4.4

SECONDARY outcome

Timeframe: Baseline, weeks 6, 12, 18, 24, 30, 36, 42 and 48

Population: Intent-to treat population with available data at each time point.

The EORTC QLQ-C30 is a validated self-rating questionnaire including 30 items used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale was scored between 0 and 100, with higher scores indicating better Global Health Status/QOL.

Outcome measures

Outcome measures
Measure	Bortezomib, Melphalan, Prednisone n=477 Participants Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Carfilzomib, Melphalan, Prednisone n=478 Participants Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores Baseline (n = 425, 425)	53.3 units on a scale Standard Deviation 21.9	53.9 units on a scale Standard Deviation 22.5
European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores Week 6 (n = 412, 407)	56.2 units on a scale Standard Deviation 19.5	61.1 units on a scale Standard Deviation 19.6
European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores Week 12 (n = 376, 389)	55.3 units on a scale Standard Deviation 19.8	62.4 units on a scale Standard Deviation 17.7
European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores Week 18 (n = 341, 369)	55.7 units on a scale Standard Deviation 18.8	63.2 units on a scale Standard Deviation 17.4
European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores Week 24 (n = 320, 345)	57.3 units on a scale Standard Deviation 17.6	63.3 units on a scale Standard Deviation 17.1
European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores Week 30 (n = 298, 317)	61.6 units on a scale Standard Deviation 17.8	63.0 units on a scale Standard Deviation 17.8
European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores Week 36 (n = 285, 308)	61.9 units on a scale Standard Deviation 17.5	64.0 units on a scale Standard Deviation 18.1
European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores Week 42 (n = 275, 288)	63.3 units on a scale Standard Deviation 17.7	65.0 units on a scale Standard Deviation 18.1
European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores Week 48 (n = 261, 265)	62.9 units on a scale Standard Deviation 18.4	65.1 units on a scale Standard Deviation 17.1

SECONDARY outcome

Population: Safety population

Adverse events (AEs)were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.03, where GRADE 1 = Mild; GRADE 2 = Moderate; GRADE 3 = Severe; GRADE 4 = Life-threatening; GRADE 5 = Fatal. A serious adverse event is an adverse event that met 1 or more of the following criteria: * Death * Life-threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * Congenital anomaly/birth defect * Important medical event that jeopardized the participant and may have required medical or surgical intervention to prevent 1 of the outcomes listed above. Treatment-related adverse events are adverse events considered related to at least 1 investigational product by the investigator, including those with unknown relationship.

Outcome measures

Outcome measures
Measure	Bortezomib, Melphalan, Prednisone n=470 Participants Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Carfilzomib, Melphalan, Prednisone n=474 Participants Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Number of Participants With Adverse Events All adverse events	454 participants	460 participants
Number of Participants With Adverse Events AEs ≥ grade 3	358 participants	354 participants
Number of Participants With Adverse Events Serious adverse events	198 participants	235 participants
Number of Participants With Adverse Events Leading to discontinuation of study drug	73 participants	83 participants
Number of Participants With Adverse Events Fatal adverse events	20 participants	31 participants
Number of Participants With Adverse Events Treatment-related adverse events (TRAEs)	431 participants	408 participants
Number of Participants With Adverse Events TRAEs ≥ grade 3	285 participants	268 participants
Number of Participants With Adverse Events Treatment-related serious adverse events	102 participants	136 participants
Number of Participants With Adverse Events TRAE leading to discontinuation of study drug	51 participants	54 participants
Number of Participants With Adverse Events Treatment-related fatal adverse events	5 participants	10 participants

Adverse Events

Bortezomib, Melphalan, Prednisone

Serious events: 198 serious events

Other events: 437 other events

Deaths: 0 deaths

Carfilzomib, Melphalan, Prednisone

Serious events: 235 serious events

Other events: 437 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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.
Publication restrictions are in place

Restriction type: OTHER