Weekly Carfilzomib-Based Regimen in Resistant Myeloma: Phase II Trial
Posted: Friday, April 23, 2021
The dosing schedule convenience of weekly carfilzomib plus cyclophosphamide and dexamethasone appears to be a bonus on top of its safety and effectiveness as a regimen for patients with relapsed or refractory multiple myeloma, especially for those who are ineligible for lenalidomide‐based therapies, according to the results of a single-arm phase II trial published in the American Journal of Hematology. Annette E. Hay, MD, of Queen’s University in Kingston, Ontario, Canada, and colleagues reported that the primary endpoint, overall response after four 28-day cycles, was 85% (68% very good partial response or better; 29% complete response or better).
The trial, MCRN‐003/CCTGMYX.1, explored the immunomodulatory drug–free regimen in 76 patients. Two of the secondary endpoints, overall survival and progression-free survival, were 27 months and 17 months, respectively, for the entire cohort. High‐risk cytogenetics correlated with worse overall response (75% vs. 97%; P = .013) and worse median overall survival (18 months vs. not reached; P = .002), with a trend toward worse median progression-free survival (14 vs. 22 months; P = .06). “Prior proteasome inhibitor or lenalidomide [treatment] did not influence overall survival or progression-free survival,” noted the team.
Also, the fact that prior proteasome inhibitor exposure was allowed was “reflective of the majority of real-world patients in the relapsed setting,” stated Dr. Hay and co-investigators. In this trial, most patients (87%) had had this exposure, yet “durable responses [were] still achievable, [as demonstrated by] the median progression-free survival of 17.2 months.”
The weekly dosing is “much more conducive to long-term therapy” than other schedules, the authors stressed. Each week, each patient received carfilzomib (20/70 mg/m2), dexamethasone 40 mg, and cyclophosphamide 300 mg/m2. Regarding safety, another secondary endpoint, the most common grade 3+ nonhematologic adverse events were of infectious (40%), vascular (17%), and cardiac nature (15%), and no unexpected toxicities were observed.
Disclosure: The study authors’ disclosure information can be found at onlinelibrary.wiley.com.