Main point #1: Despite sub-optimal response in relapsed myeloma therapy our study suggests excellent PFS for those on anti-CD38 based therapy at third-line. Main point #2: Time from myeloma diagnosis to third line therapy is an important independent predictor of long-term outcomes at third line. Multiple myeloma (MM) remains an incurable cancer and is characterized by a remitting-relapsing pattern. The choice of next line of therapy depends on patient-, disease- and treatment-related factors. The Canadian Myeloma Research Group database (CMRG-DB) hosts information in ≥10,000 individuals with plasma cell disorders across major Canadian institutions. In this retrospective study, we evaluated therapy choices and outcomes of MM patients undergoing third-line (3L) therapy utilizing the CMRG-DB platform. All relapsed MM patients in the CMRG-DB who started 3L therapy between January 2015 to December 2020 were potentially eligible. A total of 1125 patients were included. The most common 3L therapies included immunomodulatory (IMiD) agents (702 62.4%), proteasome inhibitors (PI) (491 43.6%), and anti-CD38 monoclonal antibodies (CD38 MoAb) (277 24.6%). Combinations of daratumumab + lenalidomide +/- corticosteroid produced the best responses with a median progression-free survival (mPFS) of 25.6 (95% CI 20-35.7) months. Anti-CD38 MoAb + pomalidomide +/- steroid and other PI-based regimens had a much shorter mPFS between 6 and 9 months. Adverse prognosticators were high-risk FISH, shorter time from myeloma diagnosis to 3L, triple-class exposure, prior PI exposure, and refractoriness to lenalidomide. The median overall survival (mOS) was 29.7 (95% CI 26.4-32.8) months. Our findings highlight the role of anti-CD38 MoAbs combined with lenalidomide for improvement of 3L outcomes. The results of combinations selected for 3L therapy by Canadian hematologists provide information on resource utilization and benchmark outcomes which, in turn, will be useful for multiple stakeholders in the rapidly evolving myeloma therapeutic landscape.
Louzada et al. (Sun,) studied this question.