Christopher Venner

Introduction Although daratumumab‐containing regimens improve multiple myeloma (MM) outcomes, recurrence is inevitable. Methods and Objective We performed a retrospective study using the Canadian Myeloma Research Group Database to benchmark the efficacy of carfilzomib‐ or pomalidomide‐based therapies immediately following progression on daratumumab treatment. Results We identified 178 such patients; median number of prior lines of therapy was 3, 97% triple‐class exposed, and 60% triple‐class refractory. In our cohort, 75 received a subsequent carfilzomib‐based therapy, 79 received a pomalidomide‐based therapy, and 24 received a treatment with both immunomodulatory drug (IMiD) and proteasome inhibitor (PI) using carfilzomib and/or pomalidomide. The median progression‐free survival (PFS) and overall survival (OS) for the entire cohort were 4.5 and 14.2 months, respectively. Carfilzomib‐based therapy yielded a median PFS and OS of 4.5 and 10.2 months, respectively, compared to 5.2 and 21.7 months for pomalidomide‐based therapy. Patients who received both IMiD and PI with carfilzomib and/or pomalidomide had a median PFS and OS of 4.1 and 14.5 months, respectively. Conclusion Our observations demonstrate the poor outcome of MM patients when standard regimens based on carfilzomib and/or pomalidomide are utilized directly after daratumumab‐based therapy given in the relapsed setting. Novel therapies, including immune therapies, are urgently needed to improve the outcomes of these daratumumab‐exposed patients.