Real-world outcomes of patients with multiple myeloma who reach third-line therapy: a Canadian report

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 patients with MM undergoing third-line (3L) therapy using the CMRG-DB platform. All patients with relapsed MM in the CMRG-DB who started 3L therapy between January 2015 and December 2020 were potentially eligible. A total of 1125 patients were included. The most common 3L therapies included immunomodulatory agents (702 [62.4%]), proteasome inhibitors (PIs; 491 [43.6%]), and anti-CD38 monoclonal antibodies (CD38 mAb; 277 [24.6%]). Combinations of daratumumab plus lenalidomide with or without corticosteroid produced the best responses, with a median progression-free survival (mPFS) of 25.6 months (95% confidence interval [CI], 20-35.7). An anti-CD38 mAb plus pomalidomide with or without steroid and other PI-based regimens had a much shorter mPFS, between 6 and 9 months. Adverse prognosticators were high-risk fluorescence in situ hybridization, shorter time from myeloma diagnosis to 3L, triple-class exposure, previous PI exposure, and refractoriness to lenalidomide. The median overall survival was 29.7 months (95% CI, 26.4-32.8). Our findings highlight the role of anti-CD38 mAb combined with lenalidomide for improvement of 3L outcomes. The results of combinations selected for 3L therapy by Canadian hematologists provide information on resource use and benchmark outcomes, which, in turn, will be useful for multiple stakeholders in the rapidly evolving myeloma therapeutic landscape.