Comparative safety and efficacy of DKRd versus DVRd regimens in multiple myeloma: A systematic review and meta-analysis.

7574 Background: The addition of anti-CD38 monoclonal antibodies to proteasome inhibitor–based triplet regimens, such as bortezomib-lenalidomide-dexamethasone (VRd) and carfilzomib-lenalidomide-dexamethasone (KRd), has improved depth of response, minimal residual disease (MRD) negativity, and survival in newly diagnosed multiple myeloma (NDMM). Comparative data on the efficacy and safety of daratumumab-KRd (DKRd) versus daratumumab-VRd (DVRd) are limited. We performed a systematic review and meta-analysis to evaluate these regimens in patients with NDMM. Methods: Following PRISMA guidelines, we searched PubMed, Scopus, Web of Science, and Embase from inception to November 2025 for clinical trials and observational studies of patients with NDMM treated with DVRd or DKRd. Outcomes included progression-free survival (PFS), overall survival (OS), MRD negativity, tumor response, and safety. Two independent reviewers screened studies and extracted data from each included article. Meta-analyses were done using R version 4.3.0. Heterogeneity was assessed using Cochrane's Q-test and I2. Results: Sixteen studies involving 2114 patients were included. Two-year OS was comparable between regimens (DKRd: 94.12%; DVRd 94.17%; p=0.979) while two-year PFS favored DVRd (92.76% vs 85.04%; p<0.001). At 10-5 sensitivity, post-induction MRD negativity was higher with DKRd (57.10% vs 28.60%; p=0.004). DVRd achieved superior post-induction (98.94% vs 94.62%; p<0.001) and best overall responses (98.96% vs 95.10%; p=0.019). Safety outcomes generally favored DKRd, with fewer serious adverse events (32.79% vs 60.51%; p<0.001) and grade ≥3 adverse events (77.78% vs 90.34%; p<0.001). Grade ≥3 neutropenia (50.78% vs 30.90%; p<0.001) and thrombocytopenia (25.51% versus 9.62%; p=0.005) were more common with DVRd. Treatment discontinuation rates favored DKRd (1.94% versus 8.23%; p=0.015). Mortality remained low in both arms (1.41% versus 3.00%; p=0.403). Conclusions: In NDMM, DKRd achieved deeper early MRD responses and better tolerability, whereas DVRd provided superior two-year PFS and overall response rates. Treatment selection should balance efficacy against toxicity.