MM-040: Efficacy and Safety of Carfilzomib, Dexamethasone, Daratumumab (KdD) Twice-Weekly at 56 mg/m2 and Once-Weekly at 70 mg/m2 in Relapsed or Refractory Multiple Myeloma (RRMM): Cross-Study Comparison of the CANDOR and EQUULEUS studies

Background: Regimens containing IMiDs (immunomodulatory imide drugs) are standard of care for patients with newly diagnosed multiple myeloma. The IMiD-free regimen of carfilzomib, dexamethasone, and daratumumab (KdD) is recommended by NCCN guidelines and has recently been evaluated in two studies: 1) In the randomized phase 3 CANDOR study, KdD with carfilzomib at the twice-weekly dose of 56 mg/m2 (KdD56) resulted in a 37% risk reduction of disease progression or death (vs Kd); 2) In the phase 1b EQUULEUS study, KdD with a weekly carfilzomib dose of 70 mg/m2 (KdD70) was promising. Objective: Twice-weekly KdD56 and weekly KdD70 have not been directly compared in the same trial, therefore a cross-study comparison of efficacy and safety was performed with data from the two studies just described. Methods: In order to evaluate efficacy in comparable populations, as all the patients from the KdD arm of the EQUULEUS study were required to have prior therapy with bortezomib and an IMiD, similar patients (i.e., prior treatment with bortezomib and an IMiD) were selected from the KdD arm of the CANDOR study. To adjust for selection bias, we used propensity scoring for efficacy based on prespecified prognostic baseline covariates to estimate the inverse probability of treatment weights (IPTW). Results: Before and after IPTW adjustment, overall response rate (ORR) and progression-free survival (PFS) were similar for the twice-weekly KdD56 and weekly KdD70 groups. Safety data were consistent with the known safety profiles of individual study treatments. The safety data were not adjusted as the IPTW were constructed for efficacy endpoint prognostic factors. Conclusions: We previously established in CANDOR that twice-weekly KdD56 has a favorable benefit-risk profile. This robust cross-study analysis showed evidence that KdD70 was similar to KdD56 with respect to efficacy and safety. The weekly KdD70 dosing option represents a more convenient regimen that might encourage the longer adherence important for treating patients until disease progression and thus may ultimately lead to better clinical outcomes for these patients. © 2020 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2020 ASCO Annual Meeting. All rights reserved.