Real-world comparison of Dara-VRD, VRD, and Dara-RD in transplant-ineligible older adults with newly diagnosed multiple myeloma.

Abstract

e19561 Background: Older adults with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible represent a clinically heterogeneous population frequently underrepresented in clinical trials. Treatment selection in this group must balance efficacy with tolerability, comorbidity burden, and geriatric vulnerability. While daratumumab (Dara) based regimens have improved outcomes in NDMM, real-world comparative data in older adults aged 70 years or older remain limited. Methods: We conducted a retrospective cohort study using the TriNetX research network. Patients aged 70 years or older with NDMM between 2017-2024 who received frontline bortezomib, lenalidomide, and dexamethasone (VRD); Dara-RD; or Dara-VRD, and did not undergo autologous stem cell transplant were included. Propensity score matching was performed to balance age, sex, comorbidities, and high-risk cytogenetics if available. The primary endpoint was overall survival (OS). Secondary endpoints were treatment-related adverse events with relevance to older adults, including anemia, thrombocytopenia, sepsis, and peripheral neuropathy. Survival was estimated using Kaplan–Meier methods and compared using Cox proportional hazards models. Results: A total of 1543 patients were identified (Dara-VRD: n = 227 ; Dara-RD: n = 400 ; VRD: n = 916 ). Median age at diagnosis was 75, 77, and 76 years respectively. Median OS was not reached for either the Dara-VRD or Dara-RD cohorts, with no significant difference in all cause mortality. Rates of sepsis, and peripheral neuropathy were similar between these regimens. A higher incidence of anemia and thrombocytopenia was observed in the Dara-VRD cohort (Table 1). Compared with VRD, patients treated with Dara-RD demonstrated a significantly lower all cause mortality and better OS (74% vs. 51%; log- rank p = 0.01). VRD was associated with higher rates of anemia, thrombocytopenia, and peripheral neuropathy compared with Dara-RD. On multivariable Cox analysis, Dara-RD was associated with a significantly lower risk of death compared with VRD (HR 0.66, 95% CI 0.49–0.88; p = 0.005). Conclusions: In this real-world analysis of transplant-ineligible adults aged 70 years or older with NDMM, Dara-RD was associated with improved survival and a more favorable toxicity profile compared with VRD. While Dara-VRD demonstrated comparable survival to Dara-RD, it was associated with a higher rates of cytopenias. Long-term follow-up is needed to further evaluate survival differences between Dara-VRD and Dara-RD and to identify subsets of older patients likely to derive the greatest benefit from quadruplet therapy. Outcome Dara-VRD Dara-RD P Dara-RD VRD P All-cause mortality 13% 16% 0.28 17% 29% 0.0002 Anemia (any grade) 55% 35% 0.001 37% 45% 0.02 Thrombocytopenia (any grade) 26% 16% 0.03 12% 22% 0.001 Sepsis 9% 10% 0.53 11% 12% 0.58 Peripheral neuropathy 11.5% 6% 0.09 5% 12% 0.002