Real-World Treatment Patterns and Outcomes for Patients With Relapsed/Refractory Multiple Myeloma and Prior Exposure to Lenalidomide and Proteasome Inhibitors in the United States

BACKGROUND: Successive lines of therapy (LOTs) for relapsed/refractory multiple myeloma (RRMM) are typically associated with poorer prognoses and high attrition rates. This study describes current standard-of-care treatment patterns and real-world outcomes of patients with RRMM in early LOTs. METHODS: Data were derived from the Flatiron Health Research Database for patients with an index date (RRMM treatment initiation) from January 2021 to January 2025. Eligible patients had RRMM; received 1-3 prior LOTs, including a proteasome inhibitor and lenalidomide (lenalidomide refractory if 1 prior LOT); had an Eastern Cooperative Oncology Group performance status (ECOG PS) score <3; were B-cell maturation antigen therapy naive; and could be anti-CD38 exposed, but not refractory. RESULTS: Overall, 1858 patients met the inclusion criteria: 25.4% had 1 prior LOT, 60.3% had 2 prior LOTs, and 14.3% had 3 prior LOTs; 35.7% had high-risk cytogenetics; and 29.4% were daratumumab exposed. A high degree of variability in RRMM treatment regimens was observed. At a median follow-up of 24.5 months and based on data for the first (index) regimen, median real-world progression-free survival (rwPFS) was 10.1 months, time to next LOT was 12.7 months, and median overall survival (OS) was not reached. In univariate analyses, higher ECOG PS score, high-risk cytogenetics at baseline, and lenalidomide-refractory status were among the strongest predictors of poorer rwPFS and OS. CONCLUSION: The lack of standard treatment patterns and high unmet need in patients with RRMM, as reflected by short rwPFS and time to next treatment, underscore the need for earlier use of more effective novel therapies.