ch eva luated the combination of Kyprolis with lenalidomide and dexamethasone (KRd) versus lenalidomide and dexamethasone alone (Rd) in patients with relapsed or refractory multiple myeloma who had received 1 to 3 lines of therapy (A line of therapy is a planned course of treatment [including sequential induction, transplantation, consolidation, and/or maintenance] without an interruption for lack of efficacy, such as for relapse or progressive disease). Patients who had the following were excluded from the trial: refractory to bortezomib in the most recent regimen, refractory to lenalidomide and dexamethasone in the most recent regimen, not responding to any prior regimen, creatinine clearance < 50 mL/min, ALT/AST > 3.5 × ULN and bilirubin >2× ULN, New York Heart Association Class III to IV congestive heart failure, or myocardial infarction within the last 4 months. In the KRd arm, Kyprolis was eva luated at a starting dose of 20 mg/m2, which was increased to 27 mg/m2 on Cycle 1, Day 8 onward. Kyprolis was administered as a 10-minute infusion on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle for Cycle 1 through 12. Kyprolis was dosed on Days 1, 2, 15, and 16 of each 28-day cycle from Cycle 13 through 18. Dexamethasone 40 mg was administered orally or intravenously on Days 1, 8, 15 and 22 of each cycle. Lenalidomide was given 25 mg orally on Days 1 to 21 of each 28-day cycle. The Rd treatment arm had the same regimen for lenalidomide and dexamethasone as the KRd treatment arm. Kyprolis was administered for a maximum of 18 cycles unless discontinued early for disease progression or unacceptable toxicity. Lenalidomide and dexamethasone administration could continue until progression or unacceptable toxicity. Concurrent use of thromboprophylaxis and a proton pump inhibitor were required for both arms, and antiviral prophylaxis was required for the KRd arm.
The 792 patients in Study 1 were randomized 1:1 to the KRd or Rd arm. The demographics and baseline characteristics were well-balanced between the two arms (see Table 14). Only 53% of the patients had testing for genetic mutations; a high-risk genetic mutation was identified for 12% of patients in the KRd arm and in 13% in the Rd arm.
Table 14: Demographics and Baseline Characteristics in Study 1 (Combination Therapy for Relapsed or Refractory Multiple Myeloma)
ECOG = Eastern Cooperative Oncology Group; CrCL = creatinine clearance; IgG = immunoglobulin G; ISS = International Staging System; KRd = Kyprolis, lenalidomide, and dexamethasone; Rd = lenalidomide and dexamethasone
Including 2 patients with 4 prior regimens.
Patients in the KRd arm demonstrated improved progression-free survival (PFS) compared with those in the Rd arm (HR = 0.69, with 2-sided P-value = 0.0001) as determined using standard International Myeloma Working Group (IMWG)/European Blood and Marrow Transplantation (EBMT) response criteria by an Independent Review Committee (IRC).
The median PFS was 26.3 months in the KRd arm versus 17.6 months in the Rd arm (see Table 15 and Figure 1).
The OS results were not significantly different at the interim analysis (Figure 2).
Table 15: Efficacy Outcomes in Study 1 (Combination Therapy for Relapsed or Refractory Multiple Myeloma)*
CI = confidence interval; CR = complete response; KRd = Kyprolis, lenalidomide, and dexamethasone; PFS = progression-free survival; Rd = lenalidomide and dexamethasone; sCR = stringent CR; VGPR = very good partial response
Eligible patients had 1-3 prior lines |
