(PA-393) Propensity Score–Weighted Comparison of Daratumumab-Rd versus Daratumumab-VMP, Rd, and VMP in High-Risk Multiple Myeloma: Insights from the MAIA and ALCYONE Trials

Myeloma is a common hematologic malignancy with improved outcomes, but high‐risk patients still fare poorly. In transplant‐ineligible NDMM, MAIA showed median PFS of 61.9 versus 34.4 months and OS not reached versus 65.5 months for D‐Rd versus Rd; ALCYONE reported median OS of 83.0 versus 53.6 months for D‐VMP versus VMP. No direct comparison exists.

Objective. To compare progression-free and overall survival of high-risk, transplant-ineligible NDMM patients treated with D-Rd, D-VMP, Rd, and VMP, using a propensity score–weighted analysis of pooled data from the MAIA and ALCYONE trials.

Methods:   A retrospective, IPTW‐weighted analysis of de‐identified MAIA and ALCYONE phase III data (DUA #2025-0152, YODA Project) was conducted. Only ISS III patients with high-risk cytogenetics (del(17p), amp(1q21), t(4;14), and/or t(14;16)) were included. Propensity scores from multinomial logistic regression (age > 70 years, ECOG 1–2, sex, creatinine clearance > 60 ml/min) yielded IPTW. Weighted Kaplan–Meier curves and robust Cox models compared PFS and OS between D-Rd and D-VMP

Results:   Of 103 high‐risk, transplant‐ineligible patients (24 D-Rd, 29 D-VMP, 21 Rd, 29 VMP; Table 1), IPTW balanced age ≥ 70, sex, and CLCR ≥ 60 mL/min (max SMD < 0.10)(Figure 1). Weighted 3-year PFS was 54.8% (95%CI 35% to 86%), 19.5% (95%CI 7.6% to 49.7%), 16.7% (95%CI 7.4% to 38%), and 11% (95%CI 4.1% to 29.2%) mo for D-Rd, Rd, D-VMP, and VMP (Figure 2A); median OS was 59.1, 41.0, 53.,6, and 33.0 mo, respectively (Figure 2B). In the IPTW‐Cox model for PFS, D-Rd versus VMP yielded HR 0.29 (95% CI 0.15–0.55; p< 0.001), whereas D-VMP (HR 0.92; p = 0.73) and Rd (HR 0.80; p = 0.45) were not significant. The global Wald test was χ² 14.9 (p = 0.002; c-index 0.602). For OS, no arm differed from VMP (robust Wald χ² 1.8; p = 0.60; c-index 0.561). In ECOG 1–2 patients, 2-y PFS was 57.1%, 32.0%, 35.0%, and 47.0%; 2-y OS was 57.1%, 64.0%, 70.0%, and 70.6% for D-Rd, D-VMP, VMP, and Rd, respectively (all NS). Safety results are presented in Table 2.

Conclusions:   

In this high‐risk, transplant‐ineligible cohort, D‐Rd conferred a marked PFS benefit versus VMP (HR 0.29; p < 0.001), whereas D‐VMP and Rd did not differ significantly. OS differences were non‐significant across regimens. These findings underscore the urgent need for prospective head-to-head trials—and real-world data—in elderly, high-risk myeloma patients, particularly those with impaired performance status.

Acknowledge. This study, carried out under YODA Project #2025-0152, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C. The interpretation and reporting of research using this data are solely the responsibility of the authors and do not necessarily represent the official views of the Yale University Open Data Access Project or JANSSEN RESEARCH & DEVELOPMENT, L.L.C. The original proposal can be found: https://yoda.yale.edu/data-request/2025-0152/.”