Belantamab mafodotin + pomalidomide + dexamethasone (BPd) vs daratumumab + bortezomib + dexamethasone (DVd) in relapsed/refractory multiple myeloma: An indirect comparison using patient-level data.

Abstract

7536 Background: Belantamab mafodotin (belamaf) is being studied in combination with bortezomib + dexamethasone (BVd) or pomalidomide + dexamethasone (BPd) in the phase 3 DREAMM-7 (D7; NCT04246047) and DREAMM-8 (D8; NCT04484623) trials, respectively; both enrolled patients (pts) with relapsed/refractory multiple myeloma (RRMM) who had received ≥1 prior line of therapy. D7 compared BVd vs daratumumab + bortezomib + dexamethasone (DVd); D8 compared BPd vs bortezomib + pomalidomide + dexamethasone (PVd). In both trials, belamaf combinations showed significant progression-free survival (PFS) benefits vs comparators. In D7, median PFS (95% CI) was 36.6 mo (28.4-not reached [NR]) with BVd vs 13.4 mo (11.1-17.5) with DVd (HR, 0.41; 95% CI, 0.31-0.53; P <.001). In D8, median PFS (95% CI) was NR with BPd vs 12.7 mo (9.1-18.5) with PVd (HR, 0.52; 95% CI, 0.37-0.73; P <.001). This study compared the efficacy of BPd (D8 active arm) vs DVd (D7 comparator). Methods: The overlapping D7 and D8 RRMM population was analyzed. To align cohorts, D8 BPd pts refractory to any anti-CD38 were excluded, as were D7 DVd pts without prior lenalidomide exposure or pomalidomide-refractory disease. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), minimal residual disease (MRD)–negativity rate, duration of response (DOR), overall response rate (ORR), and time to treatment discontinuation (TTD) with all treatments. This indirect comparison used inverse probability of treatment weighting to match baseline characteristics between DVd and BPd arms, estimating the average treatment effect in the treated population (IPTW-ATT). In the matched population, time-to-event analyses used the Kaplan-Meier method and Cox proportional hazards models. Results: Of 155 pts in the D8 BPd arm and 251 in the D7 DVd arm, 120 and 111, respectively, met inclusion criteria for this analysis. Baseline characteristics were generally balanced after IPTW-ATT. After adjustment, BPd significantly improved PFS vs DVd (median [95% CI], NR [21.1-NR] vs 11.1 mo [6.4-19.1]; HR, 0.41; 95% CI, 0.25-0.65; P =.0002). Median (95% CI) DOR was NR (24.9-NR) with BPd vs 10.5 mo (5.0-17.7) with DVd; adjusted MRD-negativity (CR+) rates (95% CI) were 30.2% (21-39.4) vs 5.3% (0.9-9.8), respectively (OR, 7.67; 95% CI, 3.10-22.72; P <.0001). ORR and TTD favored BPd vs DVd (ORR not significant). Conclusions: This post hoc indirect comparison analysis showed that BPd significantly improved PFS vs DVd (similar HR to BVd vs DVd in D7). Median PFS for the adjusted DVd population was similar to that reported with PVd in D8. These findings suggest that BPd may be a more effective treatment option vs DVd, warranting further studies of belamaf combinations in this population.