ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.

sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and < 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.

VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).

PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.

Safety population

ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.

sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and < 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.

VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).

PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.

Safety population

ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.

sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and < 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.

VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).

PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.

Safety population

ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.

sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and < 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.

VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).

PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.

Safety population

Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).

MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas is also required

Safety population

Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).

MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas was also required.

Safety population

Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).

MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas was also required.

Safety population

Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).

MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a >50% reduction in the size of soft tissue plasmacytomas was also required.

Safety population

Duration of response (DOR) is defined as the time from first evidence of PR or better to disease progression (PD) or death due to any cause per the IMWG-URC criteria.

PD:

• Increase of 25% from lowest response value in any of the following:

  • Serum M-component (absolute increase ≥ 0.5 g/dL) and/or
  • Urine M-component (absolute increase ≥ 200 mg/24 hours)
  • In patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL)

• Definite development of new or increase in size of existing bone lesions or soft tissue plasmacytomas

• Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.

DOR was analyzed using the Kaplan-Meier method; Participants with no documented progression or death were censored at the date of their last disease assessment.

DOR was determined based on both investigator and independent review committee response assessments.

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

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

Duration of clinical benefit was determined based on both investigator and independent review committee response assessments.

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

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

Progression-free survival was determined based on both investigator and independent review committee response assessments.

Safety population

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

Safety population

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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