Daratumumab, lenalidomide, and dexamethasone versus daratumumab, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma

Aims: Multiple myeloma (MM) is an incurable plasma cell malignancy. Daratumumab-lenalidomide-dexamethasone (DRd) and daratumumab-bortezomib-dexamethasone (DVd) are widely used in relapsed/refractory MM (RRMM) treatment. Although pivotal trials have established their efficacy, direct real-world comparisons are lacking. This study aimed to compare the effectiveness and safety of DRd and DVd in RRMM. Methods: This is a multicenter retrospective cohort study using the TriNetX Global Collaborative Network. Patients with RRMM who initiated DRd (n = 849) or DVd (n = 1380) after January 1, 2017, were identified. Propensity score matching (1:1) of balanced baseline variables yielded 795 pairs. The primary endpoint was time to next treatment (TTNT), and the secondary endpoints were 5-year overall survival (OS) and adverse events. Survival was analyzed using the Kaplan–Meier method, log-rank test, and Cox regression. Results: Median TTNT was longer with DRd than with DVd (32.6 vs. 17.7 months; hazard ratio [HR] 0.71; 95% confidence interval [CI], 0.62–0.81; p < 0.0001). Five-year OS was higher with DRd than with DVd (58.4% vs. 52.3%; HR 0.71; 95% CI, 0.59–0.86; p = 0.0003). Subgroup analyses consistently supported the DRd. Grade ≥3 neutropenia was more frequent with DRd than with DVd (27.7% vs. 12.5%), while grade ≥3 anemia was higher with the latter than with the former (12.9% vs. 7.6%). Other events occurred infrequently (<10%). Conclusion: In this large real-world cohort, DRd yielded significantly longer TTNT, improved OS, and manageable toxicity than did DVd. DRd may be the preferred regimen for RRMM; randomized head-to-head trials are warranted.