Weekly carfilzomib plus cyclophosphamide and dexamethasone in the treatment of relapsed/refractory multiple myeloma: Final results from the MCRN‐003/MYX.1 single arm phase II trial

Abstract

The MCRN‐003/CCTGMYX.1 is a single arm phase II trial of weekly carfilzomib, cyclophosphamide and dexamethasone (wKCd), exploring a convenient immunomodulator (IMiD)‐free regimen in relapsed myeloma. Weekly carfilzomib (20/70 mg/m2), dexamethasone 40 mg and cyclophosphamide 300 mg/m2 was delivered over 28‐day cycles. The primary endpoint was overall response after four cycles. Secondary endpoints included toxicity, response depth, PFS and OS. Exploratory endpoints included the impact of cytogenetics, prior therapy exposure and serum free light chain (sFLC) escape; 76 patients were accrued. The ORR was 85% (68% ≥very good partial response [VGPR] and 29% ≥complete response [CR]). The median OS and PFS were 27 and 17 months respectively. High‐risk cytogenetics conferred a worse ORR (75% vs. 97%, p = .013) and median OS (18 months vs. NR, p = .002) with a trend toward a worse median PFS (14 vs. 22 months, p = .06). Prior proteasome inhibitor (PI) or lenalidomide did not influence OS or PFS. The sFLC was noted in 15% of patients with a median PFS of 17 months when included as a progression event. The most common ≥ grade 3 non‐hematologic adverse events were infectious (40%), vascular (17%) and cardiac (15%). The wKCD is a safe and effective regimen in relapse, especially for patients ineligible for lenalidomide‐based therapies.

A descriptive cost‐analysis of MYX.1/MCRN003, a phase 2 clinical trial evaluating high‐dose weekly carfilzomib, cyclophosphamide, and dexamethasone in relapsed and refractory multiple myeloma

“…Full clinical trial results are published separately 2 . The study met its primary endpoint with an overall response rate after 4 cycles of 84% (95% confidence interval: 76%‐92%) and the best overall response rate (ORR) was 85% (95% confidence interval: 77%‐93%).…”

“…It was designed to test the efficacy and safety of high‐dose weekly carfilzomib (Krypolis), cyclophosphamide, and dexamethasone (wKCD) in patients with relapsed and refractory multiple myeloma (RRMM) who had previously received 1‐3 prior lines of therapy. The study met its primary objective of overall response rate greater than 80% (ORR 84%) after four cycles of wKCD 2‐4 . This regimen was intentionally designed to minimize the cost of chemotherapy and prioritize the ease of administration for patients.…”

Carfilzomib usage patterns and outcomes in patients with relapsed multiple myeloma: A multi‐institutional report from the Canadian Myeloma Research Group (CMRG) Database

“…Both progression-free survival (PFS) (26. with a comparable safety profile in this more heavily pre-treated population [14]. phase II trial of patients with one to three prior lines [17], and median PFS of 20.7 months compared to 15.2 months for Kd in a randomized phase trial [18].…”

“…Isatuximab, carfilzomib, and dexamethasone (IKd) was compared to Kd in the IKEMA trial, recently presented with PFS of 35.7 months for IKd and 19.2 months for Kd, respectively [16]. Lastly, the combination of carfilzomib with cyclophosphamide and dexamethasone (KCd) has been studied, with median PFS of 17.2 months reported in a single‐arm phase II trial of patients with one to three prior lines [17], and median PFS of 20.7 months compared to 15.2 months for Kd in a randomized phase trial [18].…”

“…Carfilzomib usage in patients, n (percentage) outside clinical trials by (A) lines of treatment and (B) years of study period.patients treated with KCd were on clinical trial (mostly the Canadian Phase II MCRN003/MYX1 trial[17]). …”