Real-World Treatment Outcomes of Different Sequencing Options with Daratumumab, Lenalidomide, and Dexamethasone in Patients with Transplant-Ineligible Multiple Myeloma in Japan

Background/Objectives: Treatment options for multiple myeloma (MM) have increased in recent years. Daratumumab, a human IgG1 kappa monoclonal antibody targeting CD38, is available in Japan for transplant-ineligible newly diagnosed MM (NDMM) when used in combination with lenalidomide + dexamethasone (DRd). There is limited evidence on when DRd should be introduced in the treatment sequence (i.e., as first-line [1L] or second-line [2L] and later). Methods: We conducted a retrospective study using claims data from Japan to identify the optimal treatment strategy for DRd in patients with transplant-ineligible NDMM in real-world clinical practice. Patients were stratified into 1L, 2L, and third-line or later (>= 3L) groups based on their DRd line of treatment. Study outcomes included the impact of DRd treatment line on overall survival (OS) and time to next treatment (TTNT). Using Cox regression analysis, potential associations between patient characteristics and OS and TTNT were investigated. Results: In total, 344 patients with MM who received DRd treatment were evaluated (208 received 1L, 78 received 2L, and 58 received >= 3L). There was a trend toward improved OS from the time of MM diagnosis (inverse hazard ratio [HR] 0.658; 95% confidence interval [CI] 0.278, 1.563) and prolonged TTNT from the first DRd administration (inverse HR of 0.746; 95% CI: 0.481, 1.149) with 1L versus 2L DRd. Conclusions: The effect of treatment line (1L and 2L) was consistent after adjusting for factors associated with OS and TTNT. These results suggest that the use of 1L DRd may provide the best outcomes for patients with transplant-ineligible NDMM.