Multiple Myeloma
Conditions
Brief summary
The purpose of the study is to assess the safety, tolerability and activity of a once-weekly regimen of carfilzomib in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma.
Interventions
DRUGCarfilzomib
Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
DRUGLenalidomide
Administered orally once daily on days 1-21 of each 28-day cycle.
DRUGDexamethasone
Administered by mouth or IV at 40 mg on days 1, 8, and 15 of each 28-day cycle and on day 22 of cycles 1 to 8.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Newly diagnosed or relapsed multiple myeloma 2. Measureable disease by serum M protein, or urine M protein, or serum free light chain (SFLC) and an abnormal serum kappa lambda ratio (for subjects without detectable serum or urine M-protein), or serum quantitative immunoglobulin A (glgA) (for immunoglobulin (Ig) A subjects whose disease can only be reliable measured by qlgA). 3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2 4. Left ventricular ejection fraction (LVEF) ≥ 40% Key
Exclusion criteria
1. Waldenström macroglobulinemia 2. For newly diagnosed multiple myeloma: multiple myeloma of IgM subtype 3. For relapsed disease: 1. If treated with a lenalidomide and dexamethasone combination, progression during the first 3 months after initiating treatment. 2. Any progression during treatment if the lenalidomide and dexamethasone regimen was the most recent line of therapy. 3. Any prior treatment with carfilzomib 4. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 5. Plasma cell leukemia (\> 2.0 × 10\^9/L circulating plasma cells by standard differential) 6. Myelodysplastic syndrome 7. Amyloidosis 8. Prior treatment with carfilzomib or oprozomib
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | From the first dose of any study drug up to 30 days after the last dose of any study drug; median (range) duration of treatment with carfilzomib was 32 (1.1, 76.7) weeks in RRMM participants and 26 (1.0, 94.4) weeks in NDMM participants. | Safety and tolerability were evaluated according to the type, incidence, and severity of adverse events. An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria: * fatal * life threatening * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event The severity of each AE was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death. |
| Change From Baseline in Hemoglobin Levels | Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15 | — |
| Change From Baseline in Platelet Count | Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15 | — |
| Change From Baseline in Neutrophil Count | Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15 | — |
| Change From Baseline in Bilirubin | Baseline and Cycle 2 day 1 | — |
| Change From Baseline in Creatinine | Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group | Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion | — |
| Duration of Response (DOR) | From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants. | Duration of response (DOR) was calculated for participants who achieved a confirmed PR or better based on Investigator assessment and according to the IMWG URC. Duration of overall response is defined as the time from first documentation of response to disease progression or death due to any cause. DOR was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after \> 1 consecutively missed disease assessment visit, were lost to follow-up, or withdrew consent were censored at the date of last disease assessment. |
| Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group | Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion | — |
| Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group | Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion | — |
| Overall Response Rate (ORR) | Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants. | Response was determined by the investigator based on the International Myeloma Working Group Uniform Response Criteria (IMWG URC). ORR was defined as the percentage of participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Responses must have been confirmed in 2 consecutive assessments at any time prior to initiation of any new therapy. Disease assessments included serum protein electrophoresis (SPEP) with immunofixation, urine protein electrophoresis (UPEP; 24-hour assessment) with immunofixation, serum free light chain (SFLC), quantitative immunoglobulins, bone marrow aspirates to determine percent plasma cell involvement, and skeletal imaging for plasmacytoma evaluation. |
| Complete Response Rate (CRR) | Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants. | Complete Response Rate (CRR) is defined as the percentage of participants who achieved a best overall response of either stringent complete response (sCR) or complete response (CR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM) CR: Negative serum and urine immunofixation, disappearance of any soft tissue plasmacytomas, \< 5% plasma cells in BM, and normal SFLC ratio in participants with measurable disease only by SFLC. |
| Progression-free Survival (PFS) | From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants. | PFS is defined as the time from the first day of study treatment to the earlier of disease progression or death due to any cause. Disease progression was determined by the investigator according to IMWG-URC. Progressive Disease (PD): Increase of 25% from lowest value in serum M-component (absolute increase ≥ 0.5 g/dL), urine M-component (absolute increase ≥ 200 mg per 24 hours) and/or the difference between involved and uninvolved FLC levels (absolute increase \>10 mg/dL) in patients without measurable serum and urine M-protein levels, and/or any new or increase in size of bone lesions or soft tissue plasmacytomas, or development of hypercalcemia. PFS was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after \> 1 consecutively missed assessment visit, were lost to follow-up or withdrew consent were censored at the date of last disease assessment. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 21 centers in the United States. The study had 2 parts: dose-evaluation and dose-expansion.
Pre-assignment details
A Cohort Safety Review Committee (CSRC) reviewed all safety data and made recommendations regarding ongoing enrollment and opening of subsequent cohorts during the dose-evaluation component. The CSRC also selected the dose regimens evaluated in the dose-expansion component.
Participants by arm
| Arm | Count |
|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death.
Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. | 10 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death.
Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. | 12 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death.
Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. | 34 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² Participants with newly diagnosed multiple myeloma (NDMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death.
Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1 day 1, 56 mg/m² on cycle 1 days 8 and 15, and then 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. | 9 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death.
Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. | 9 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death.
Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. | 33 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Specified Criteria | 5 | 7 | 27 | 7 | 5 | 21 |
| Overall Study | Sponsor Decision | 0 | 0 | 1 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 2 | 1 | 3 | 9 |
Baseline characteristics
| Characteristic | RRMM Dose-evaluation: Carfilzomib 70 mg/m² | RRMM Dose-expansion: Carfilzomib 70 mg/m² | NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | NDMM Dose-expansion: Carfilzomib 70 mg/m² | NDMM Dose-expansion: Carfilzomib 56 mg/m² | RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.4 years STANDARD_DEVIATION 8.1 | 61.9 years STANDARD_DEVIATION 11.2 | 59.0 years STANDARD_DEVIATION 14 | 61.8 years STANDARD_DEVIATION 6.5 | 60.4 years STANDARD_DEVIATION 10.7 | 67.4 years STANDARD_DEVIATION 9.3 | 61.7 years STANDARD_DEVIATION 10.6 |
| Age, Customized 65 to 74 years | 6 Participants | 10 Participants | 3 Participants | 3 Participants | 9 Participants | 5 Participants | 36 Participants |
| Age, Customized < 65 years | 5 Participants | 20 Participants | 6 Participants | 6 Participants | 23 Participants | 4 Participants | 64 Participants |
| Age, Customized ≥ 75 years | 1 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 30 Participants | 9 Participants | 7 Participants | 30 Participants | 10 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 14 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 24 Participants | 7 Participants | 7 Participants | 28 Participants | 8 Participants | 81 Participants |
| Sex: Female, Male Female | 5 Participants | 15 Participants | 3 Participants | 3 Participants | 16 Participants | 3 Participants | 45 Participants |
| Sex: Female, Male Male | 7 Participants | 19 Participants | 6 Participants | 6 Participants | 17 Participants | 7 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 12 | 2 / 34 | 0 / 9 | 0 / 9 | 0 / 33 |
| other Total, other adverse events | 10 / 10 | 12 / 12 | 33 / 34 | 9 / 9 | 9 / 9 | 33 / 33 |
| serious Total, serious adverse events | 4 / 10 | 5 / 12 | 10 / 34 | 3 / 9 | 3 / 9 | 11 / 33 |
Outcome results
Primary
Change From Baseline in Bilirubin
Time frame: Baseline and Cycle 2 day 1
Population: Participants in the safety analysis set with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Bilirubin | Baseline | 8.55 µmol/L | Standard Deviation 3.78 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Bilirubin | Change from Baseline to Cycle 2 Day 1 | 0.86 µmol/L | Standard Deviation 3.25 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Bilirubin | Baseline | 9.98 µmol/L | Standard Deviation 4.72 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Bilirubin | Change from Baseline to Cycle 2 Day 1 | 1.00 µmol/L | Standard Deviation 3.68 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Bilirubin | Baseline | 9.10 µmol/L | Standard Deviation 4.76 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Bilirubin | Change from Baseline to Cycle 2 Day 1 | 1.34 µmol/L | Standard Deviation 3.52 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Bilirubin | Baseline | 10.26 µmol/L | Standard Deviation 4.38 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Bilirubin | Change from Baseline to Cycle 2 Day 1 | 3.42 µmol/L | Standard Deviation 5.56 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Bilirubin | Baseline | 6.84 µmol/L | Standard Deviation 4.01 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Bilirubin | Change from Baseline to Cycle 2 Day 1 | 0.49 µmol/L | Standard Deviation 2.91 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Bilirubin | Baseline | 7.16 µmol/L | Standard Deviation 3.29 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Bilirubin | Change from Baseline to Cycle 2 Day 1 | 1.21 µmol/L | Standard Deviation 3.1 |
Primary
Change From Baseline in Creatinine
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Population: Participants in the safety analysis set with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 15 | -4.42 µmol/L | Standard Deviation 7.92 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Baseline | 80.18 µmol/L | Standard Deviation 18.57 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 15 | -6.28 µmol/L | Standard Deviation 10.29 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 8 | -2.65 µmol/L | Standard Deviation 5.05 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 8 | -6.45 µmol/L | Standard Deviation 4.97 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 1 | -3.80 µmol/L | Standard Deviation 6.81 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 8 | -11.09 µmol/L | Standard Deviation 12.7 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 15 | -4.60 µmol/L | Standard Deviation 11.32 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Baseline | 82.88 µmol/L | Standard Deviation 22.01 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 1 | -7.74 µmol/L | Standard Deviation 11.98 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 15 | -13.26 µmol/L | Standard Deviation 9.05 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 8 | -5.30 µmol/L | Standard Deviation 10.29 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 8 | 2.09 µmol/L | Standard Deviation 8.31 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Baseline | 79.09 µmol/L | Standard Deviation 17.61 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 15 | -1.85 µmol/L | Standard Deviation 12.69 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 1 | -1.44 µmol/L | Standard Deviation 9.66 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 8 | 1.85 µmol/L | Standard Deviation 10.95 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 15 | 4.88 µmol/L | Standard Deviation 13.78 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 1 | -10.39 µmol/L | Standard Deviation 10.05 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Creatinine | Baseline | 75.80 µmol/L | Standard Deviation 7.78 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 15 | 3.65 µmol/L | Standard Deviation 27.29 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 8 | -1.22 µmol/L | Standard Deviation 8.25 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 15 | -12.38 µmol/L | Standard Deviation 6.9 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 8 | -12.27 µmol/L | Standard Deviation 8.2 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Baseline | 95.37 µmol/L | Standard Deviation 41.17 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 8 | -20.08 µmol/L | Standard Deviation 37.86 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 1 | -17.17 µmol/L | Standard Deviation 36.71 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 15 | -21.85 µmol/L | Standard Deviation 39.17 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 15 | 29.39 µmol/L | Standard Deviation 130.24 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 8 | -8.51 µmol/L | Standard Deviation 29.44 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 15 | 0.42 µmol/L | Standard Deviation 17.59 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 1 | -4.31 µmol/L | Standard Deviation 9.84 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Baseline | 80.60 µmol/L | Standard Deviation 21.56 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 8 | -4.32 µmol/L | Standard Deviation 9.36 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 2 Day 15 | -1.99 µmol/L | Standard Deviation 18.08 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Creatinine | Change from Baseline to Cycle 1 Day 8 | -0.22 µmol/L | Standard Deviation 12.89 |
Primary
Change From Baseline in Hemoglobin Levels
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Population: Participants in the safety analysis set with available data at Baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Baseline | 116.90 g/L | Standard Deviation 14.58 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 8 | -1.50 g/L | Standard Deviation 7.52 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 15 | -6.90 g/L | Standard Deviation 8.61 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 1 | -5.70 g/L | Standard Deviation 9.78 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 8 | -6.00 g/L | Standard Deviation 11.91 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 15 | -8.50 g/L | Standard Deviation 12.47 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 8 | -3.33 g/L | Standard Deviation 6.39 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 1 | -9.25 g/L | Standard Deviation 8.67 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 15 | -11.33 g/L | Standard Deviation 8.04 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Baseline | 120.67 g/L | Standard Deviation 13.51 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 15 | -9.50 g/L | Standard Deviation 6.29 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 8 | -8.17 g/L | Standard Deviation 9 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 15 | -8.45 g/L | Standard Deviation 10.08 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 8 | -5.59 g/L | Standard Deviation 8.35 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 1 | -7.38 g/L | Standard Deviation 7.76 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 15 | -5.10 g/L | Standard Deviation 7.88 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Baseline | 123.24 g/L | Standard Deviation 16.57 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 8 | -0.91 g/L | Standard Deviation 5.46 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 1 | -3.75 g/L | Standard Deviation 12.65 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 8 | -1.25 g/L | Standard Deviation 8.17 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 15 | -1.75 g/L | Standard Deviation 12.7 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 15 | 0.00 g/L | Standard Deviation 14.05 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 8 | -0.13 g/L | Standard Deviation 14.64 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Hemoglobin Levels | Baseline | 111.50 g/L | Standard Deviation 18.04 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Baseline | 120.00 g/L | Standard Deviation 20.96 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 8 | -2.86 g/L | Standard Deviation 8.49 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 8 | -5.56 g/L | Standard Deviation 6.11 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 15 | -6.50 g/L | Standard Deviation 10.2 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 1 | -3.29 g/L | Standard Deviation 9.6 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 15 | -5.14 g/L | Standard Deviation 13.58 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 1 | 2.19 g/L | Standard Deviation 10.59 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 15 | -5.64 g/L | Standard Deviation 9.1 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 8 | 4.19 g/L | Standard Deviation 12.41 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 2 Day 15 | 2.97 g/L | Standard Deviation 13.04 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Change from Baseline to Cycle 1 Day 8 | -1.82 g/L | Standard Deviation 7.21 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Hemoglobin Levels | Baseline | 113.21 g/L | Standard Deviation 16.66 |
Primary
Change From Baseline in Neutrophil Count
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Population: Participants in the safety analysis set with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Baseline | 2.53 10^9 cells/L | Standard Deviation 1.01 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 8 | 0.02 10^9 cells/L | Standard Deviation 0.82 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 15 | 0.28 10^9 cells/L | Standard Deviation 1.14 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 1 | 0.36 10^9 cells/L | Standard Deviation 1.99 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 8 | 0.18 10^9 cells/L | Standard Deviation 0.68 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 15 | -0.30 10^9 cells/L | Standard Deviation 0.71 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 8 | 0.03 10^9 cells/L | Standard Deviation 1.87 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 1 | -0.33 10^9 cells/L | Standard Deviation 1.59 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 15 | -0.54 10^9 cells/L | Standard Deviation 1.69 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Baseline | 3.40 10^9 cells/L | Standard Deviation 1.54 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 15 | -0.09 10^9 cells/L | Standard Deviation 1.94 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 8 | -0.67 10^9 cells/L | Standard Deviation 1.28 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 15 | -0.06 10^9 cells/L | Standard Deviation 1.25 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 8 | 0.63 10^9 cells/L | Standard Deviation 1.08 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 1 | 0.16 10^9 cells/L | Standard Deviation 1.15 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 15 | 0.81 10^9 cells/L | Standard Deviation 1.09 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Baseline | 2.72 10^9 cells/L | Standard Deviation 0.94 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 8 | 0.97 10^9 cells/L | Standard Deviation 1.19 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 1 | 0.02 10^9 cells/L | Standard Deviation 0.58 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 8 | 0.59 10^9 cells/L | Standard Deviation 1.2 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 15 | 1.08 10^9 cells/L | Standard Deviation 1.53 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 15 | 0.33 10^9 cells/L | Standard Deviation 0.53 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 8 | 0.57 10^9 cells/L | Standard Deviation 1.05 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Neutrophil Count | Baseline | 3.04 10^9 cells/L | Standard Deviation 0.73 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Baseline | 3.24 10^9 cells/L | Standard Deviation 2.24 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 8 | 0.46 10^9 cells/L | Standard Deviation 2.49 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 8 | -0.19 10^9 cells/L | Standard Deviation 1.25 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 15 | 0.43 10^9 cells/L | Standard Deviation 1.83 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 1 | 0.09 10^9 cells/L | Standard Deviation 2.46 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 15 | 0.56 10^9 cells/L | Standard Deviation 2.92 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 1 | 0.18 10^9 cells/L | Standard Deviation 0.95 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 15 | 0.09 10^9 cells/L | Standard Deviation 1.48 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 8 | 0.41 10^9 cells/L | Standard Deviation 1.25 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 2 Day 15 | 0.42 10^9 cells/L | Standard Deviation 2 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Change from Baseline to Cycle 1 Day 8 | 0.37 10^9 cells/L | Standard Deviation 1.29 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Neutrophil Count | Baseline | 3.26 10^9 cells/L | Standard Deviation 1.46 |
Primary
Change From Baseline in Platelet Count
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Population: Participants in the safety analysis set with available data at Baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 15 | -58.60 10^9 cells/L | Standard Deviation 32.76 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 15 | -44.40 10^9 cells/L | Standard Deviation 21.48 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 8 | -44.10 10^9 cells/L | Standard Deviation 38.14 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 1 | 55.00 10^9 cells/L | Standard Deviation 38.61 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Baseline | 151.60 10^9 cells/L | Standard Deviation 54.4 |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 8 | -12.90 10^9 cells/L | Standard Deviation 29.88 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Baseline | 202.50 10^9 cells/L | Standard Deviation 67.13 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 8 | -74.75 10^9 cells/L | Standard Deviation 86.91 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 8 | -49.50 10^9 cells/L | Standard Deviation 58.9 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 15 | -63.25 10^9 cells/L | Standard Deviation 72.53 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 1 | 68.67 10^9 cells/L | Standard Deviation 84.62 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 15 | -66.83 10^9 cells/L | Standard Deviation 87.14 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 15 | -66.39 10^9 cells/L | Standard Deviation 38.3 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Baseline | 172.38 10^9 cells/L | Standard Deviation 33.7 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 8 | -17.36 10^9 cells/L | Standard Deviation 21.75 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 1 | 44.84 10^9 cells/L | Standard Deviation 52.82 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 8 | -71.06 10^9 cells/L | Standard Deviation 37.93 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 15 | -60.13 10^9 cells/L | Standard Deviation 43.37 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 8 | 2.38 10^9 cells/L | Standard Deviation 63.66 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 15 | -21.25 10^9 cells/L | Standard Deviation 82.11 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 1 | 141.75 10^9 cells/L | Standard Deviation 92.68 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Platelet Count | Baseline | 214.00 10^9 cells/L | Standard Deviation 79.22 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 8 | -28.00 10^9 cells/L | Standard Deviation 111.1 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 15 | -23.25 10^9 cells/L | Standard Deviation 116.67 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 8 | -51.11 10^9 cells/L | Standard Deviation 42.1 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 15 | -76.14 10^9 cells/L | Standard Deviation 116.02 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 8 | -106.29 10^9 cells/L | Standard Deviation 130.18 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 15 | -101.88 10^9 cells/L | Standard Deviation 84.66 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Baseline | 242.89 10^9 cells/L | Standard Deviation 99.24 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 1 | 152.00 10^9 cells/L | Standard Deviation 244.5 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 15 | -44.19 10^9 cells/L | Standard Deviation 64.73 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 15 | -53.39 10^9 cells/L | Standard Deviation 43.6 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 1 | 111.06 10^9 cells/L | Standard Deviation 84.26 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 1 Day 8 | -21.42 10^9 cells/L | Standard Deviation 36.4 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Baseline | 233.03 10^9 cells/L | Standard Deviation 67.76 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Change From Baseline in Platelet Count | Change from Baseline to Cycle 2 Day 8 | -52.78 10^9 cells/L | Standard Deviation 60.7 |
Primary
Number of Participants With Adverse Events (AEs)
Safety and tolerability were evaluated according to the type, incidence, and severity of adverse events. An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria: * fatal * life threatening * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event The severity of each AE was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.
Time frame: From the first dose of any study drug up to 30 days after the last dose of any study drug; median (range) duration of treatment with carfilzomib was 32 (1.1, 76.7) weeks in RRMM participants and 26 (1.0, 94.4) weeks in NDMM participants.
Population: All participants who received at least 1 dose of study drug (safety analysis set).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of lenalidomide | 1 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 1 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Serious adverse events | 4 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of dexamethasone | 1 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Any adverse event (AE) | 10 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of dexamethasone | 1 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of carfilzomib | 1 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related AEs Grade ≥ 3 | 6 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events (TRAE) | 9 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related fatal adverse events | 0 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | AE Grade ≥ 3 | 7 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of carfilzomib | 1 Participants |
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of lenalidomide | 1 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Any adverse event (AE) | 12 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related AEs Grade ≥ 3 | 8 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events (TRAE) | 11 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related fatal adverse events | 0 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AE Grade ≥ 3 | 9 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of dexamethasone | 1 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Serious adverse events | 5 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of lenalidomide | 1 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of carfilzomib | 2 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of carfilzomib | 1 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of lenalidomide | 2 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of dexamethasone | 2 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 2 Participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of dexamethasone | 5 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events (TRAE) | 30 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of lenalidomide | 5 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AE Grade ≥ 3 | 23 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 6 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related fatal adverse events | 2 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related AEs Grade ≥ 3 | 18 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of dexamethasone | 5 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of lenalidomide | 5 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Any adverse event (AE) | 34 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of carfilzomib | 5 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Serious adverse events | 10 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of carfilzomib | 5 Participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 2 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | Any adverse event (AE) | 9 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | AE Grade ≥ 3 | 5 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | Serious adverse events | 3 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of carfilzomib | 0 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of dexamethasone | 0 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of lenalidomide | 0 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events (TRAE) | 9 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related AEs Grade ≥ 3 | 5 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 1 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of carfilzomib | 0 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of lenalidomide | 0 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of dexamethasone | 0 Participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related fatal adverse events | 0 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Any adverse event (AE) | 9 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of lenalidomide | 2 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of carfilzomib | 2 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 3 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AE Grade ≥ 3 | 6 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related fatal adverse events | 0 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of dexamethasone | 2 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of carfilzomib | 2 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of dexamethasone | 2 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events (TRAE) | 9 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of lenalidomide | 2 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Serious adverse events | 3 Participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related AEs Grade ≥ 3 | 5 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related fatal adverse events | 0 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of lenalidomide | 2 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 8 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of carfilzomib | 1 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related AEs Grade ≥ 3 | 18 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of carfilzomib | 1 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Serious adverse events | 11 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of dexamethasone | 2 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of lenalidomide | 2 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | AE Grade ≥ 3 | 21 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | TRAEs leading to discontinuation of dexamethasone | 2 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events (TRAE) | 32 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Number of Participants With Adverse Events (AEs) | Any adverse event (AE) | 33 Participants |
Secondary
Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Time frame: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
Population: Participants who received at least 1 dose of study drug who had sufficient carfilzomib exposure and plasma concentration versus time data for the estimation of pharmacokinetic parameters by a non-compartmental analysis on day 8 of cycle 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group | 4150 hr*ng/mL | Standard Deviation 17500 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group | 9130 hr*ng/mL | Standard Deviation 32800 |
Secondary
Complete Response Rate (CRR)
Complete Response Rate (CRR) is defined as the percentage of participants who achieved a best overall response of either stringent complete response (sCR) or complete response (CR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM) CR: Negative serum and urine immunofixation, disappearance of any soft tissue plasmacytomas, \< 5% plasma cells in BM, and normal SFLC ratio in participants with measurable disease only by SFLC.
Time frame: Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Complete Response Rate (CRR) | 20.0 percentage of participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Complete Response Rate (CRR) | 16.7 percentage of participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Complete Response Rate (CRR) | 26.5 percentage of participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Complete Response Rate (CRR) | 23.9 percentage of participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Complete Response Rate (CRR) | 22.2 percentage of participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Complete Response Rate (CRR) | 11.1 percentage of participants |
| NDMM: Combined Carfilzomib 70 mg/m² | Complete Response Rate (CRR) | 16.7 percentage of participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Complete Response Rate (CRR) | 33.3 percentage of participants |
Secondary
Duration of Response (DOR)
Duration of response (DOR) was calculated for participants who achieved a confirmed PR or better based on Investigator assessment and according to the IMWG URC. Duration of overall response is defined as the time from first documentation of response to disease progression or death due to any cause. DOR was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after \> 1 consecutively missed disease assessment visit, were lost to follow-up, or withdrew consent were censored at the date of last disease assessment.
Time frame: From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
Population: Participants who received at least 1 dose of study drug with an overall response of PR or better.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Duration of Response (DOR) | NA months |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Duration of Response (DOR) | NA months |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Duration of Response (DOR) | NA months |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Duration of Response (DOR) | NA months |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Duration of Response (DOR) | NA months |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Duration of Response (DOR) | NA months |
| NDMM: Combined Carfilzomib 70 mg/m² | Duration of Response (DOR) | NA months |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Duration of Response (DOR) | NA months |
Secondary
Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Time frame: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
Population: Participants who received at least 1 dose of study drug who had sufficient carfilzomib exposure and plasma concentration versus time data for the estimation of pharmacokinetic parameters by a non-compartmental analysis on day 8 of cycle 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group | 11700 ng/mL | Standard Deviation 67300 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group | 12400 ng/mL | Standard Deviation 45000 |
Secondary
Overall Response Rate (ORR)
Response was determined by the investigator based on the International Myeloma Working Group Uniform Response Criteria (IMWG URC). ORR was defined as the percentage of participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Responses must have been confirmed in 2 consecutive assessments at any time prior to initiation of any new therapy. Disease assessments included serum protein electrophoresis (SPEP) with immunofixation, urine protein electrophoresis (UPEP; 24-hour assessment) with immunofixation, serum free light chain (SFLC), quantitative immunoglobulins, bone marrow aspirates to determine percent plasma cell involvement, and skeletal imaging for plasmacytoma evaluation.
Time frame: Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Overall Response Rate (ORR) | 90.0 percentage of participants |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Overall Response Rate (ORR) | 91.7 percentage of participants |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Overall Response Rate (ORR) | 88.2 percentage of participants |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Overall Response Rate (ORR) | 89.1 percentage of participants |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Overall Response Rate (ORR) | 88.9 percentage of participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Overall Response Rate (ORR) | 77.8 percentage of participants |
| NDMM: Combined Carfilzomib 70 mg/m² | Overall Response Rate (ORR) | 83.3 percentage of participants |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Overall Response Rate (ORR) | 97.0 percentage of participants |
Secondary
Progression-free Survival (PFS)
PFS is defined as the time from the first day of study treatment to the earlier of disease progression or death due to any cause. Disease progression was determined by the investigator according to IMWG-URC. Progressive Disease (PD): Increase of 25% from lowest value in serum M-component (absolute increase ≥ 0.5 g/dL), urine M-component (absolute increase ≥ 200 mg per 24 hours) and/or the difference between involved and uninvolved FLC levels (absolute increase \>10 mg/dL) in patients without measurable serum and urine M-protein levels, and/or any new or increase in size of bone lesions or soft tissue plasmacytomas, or development of hypercalcemia. PFS was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after \> 1 consecutively missed assessment visit, were lost to follow-up or withdrew consent were censored at the date of last disease assessment.
Time frame: From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
Population: Participants who received at least 1 dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Progression-free Survival (PFS) | NA months |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Progression-free Survival (PFS) | NA months |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | Progression-free Survival (PFS) | NA months |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | Progression-free Survival (PFS) | NA months |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | Progression-free Survival (PFS) | NA months |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Progression-free Survival (PFS) | NA months |
| NDMM: Combined Carfilzomib 70 mg/m² | Progression-free Survival (PFS) | NA months |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | Progression-free Survival (PFS) | NA months |
Secondary
Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Time frame: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
Population: Participants who received at least 1 dose of study drug who had sufficient carfilzomib exposure and plasma concentration versus time data for the estimation of pharmacokinetic parameters by a non-compartmental analysis on day 8 of cycle 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group | 0.28 hours |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group | 0.27 hours |