7567 Background: Older patients with newly diagnosed multiple myeloma (MM) frequently experience early treatment discontinuation due to toxicity, comorbidities, and frailty. Although randomized trials support anti-CD38-based induction regimens, real-world comparative data evaluating early clinical outcomes in older, transplant-ineligible patients remain limited. Methods: We conducted a retrospective, multi-institutional cohort study using TriNetX, including adults aged ≥70 years with newly diagnosed MM after 2019 who initiated treatment within two months of diagnosis and did not undergo autologous stem cell transplantation. We performed two matched comparative analyses: Dara-RVd versus RVd and Dara-RVd versus Dara-Rd. We first assessed the proportion of patients initiating second-line therapy at 12 and 24 months. Analyses were then restricted to patients who remained on first-line therapy for at least one year to evaluate early clinical outcomes, including all-cause mortality and healthcare utilization (emergency department ED visits, ICU admissions, and bacterial infection or sepsis). Matching included demographics, comorbidities, presence of extramedullary plasmacytoma, and baseline laboratory values (LDH, albumin, β2 microglobulin, creatinine, and hemoglobin), BMI and recent hospitalization. Hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CI) were reported. Results: Compared with RVd, Dara-RVd showed similar second-line initiation within 12 months (13% vs 14%; p=0.857) and 24 months (14% vs 19%; p=0.086). Among 768 matched patients per group who remained on first-line therapy at one year (mean age 75 years), Dara-RVd was associated with lower 1-year all-cause mortality (12% vs 17%; HR 0.70; 95% CI 0.55–0.90) and reduced healthcare utilization, including ≥1 ED visit (30% vs 36%; RR 0.85; 95% CI 0.73–0.98) and ICU admission (8% vs 12%; RR 0.70; 95% CI 0.52–0.95), while infection rates were similar. Compared with Dara-Rd, Dara-RVd showed comparable second-line initiation within 12 months (13% vs 10%; p=0.126) and 24 months (15% vs 11%; p=0.218). Among 511 matched patients per group who remained on first-line therapy at one year (mean age 76 years), no significant differences were observed in 1-year all-cause mortality or healthcare utilization outcomes. Conclusions: In older, transplant-ineligible patients with newly diagnosed MM who remained on therapy at one year, Dara-RVd was associated with improved early survival and lower healthcare utilization compared with RVd, while outcomes were comparable to Dara-Rd. Despite the retrospective design and potential unmeasured confounding, these findings support daratumumab-based regimens in older patients. Prospective studies incorporating frailty and early treatment discontinuation are needed to better define optimal induction strategies.
Çetin et al. (Thu,) studied this question.