PFS2 outcomes by prior therapy from DREAMM-8: A phase 3 study assessing belantamab mafodotin (belamaf), pomalidomide, and dexamethasone (BPd) vs pomalidomide, bortezomib, and dexamethasone (PVd) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).

Abstract

7566 Background: B-cell maturation antigen (BCMA)–directed therapies have transformed the treatment landscape in RRMM. Belamaf, a BCMA-targeting antibody-drug conjugate, in combination with Pd significantly improved progression-free survival (PFS) vs PVd (hazard ratio [HR], 0.52; 95% CI, 0.37-0.73; P <0.001) in pts with RRMM in DREAMM-8 (median follow-up, 22 mo). This PFS benefit was maintained with extended follow-up (HR, 0.49; 95% CI, 0.36-0.67; median follow-up 36 mo); median PFS2 also favored BPd vs PVd (47.1 vs 21.7 mo, respectively; HR, 0.52; 95% CI, 0.38-0.70), indicating sustained clinical benefit over time. We report PFS2 outcomes from DREAMM-8 in subgroups based on prior therapy to further understand the long-term impact of BPd and inform treatment sequencing. Methods: DREAMM-8 (NCT04484623) is a phase 3, randomized, open-label study evaluating BPd vs PVd in pts with RRMM with ≥1 prior line of therapy including lenalidomide (LEN). Pts could not have received prior BMCA-targeted therapy. PFS2 was defined as time from randomization to disease progression after initiation of subsequent antimyeloma therapy or death. PFS2 was assessed based on prior-treatment subgroups. Results: In the BPd arm (DCO: Jul 7, 2025; median follow-up, 36 mo), PFS2 benefit was maintained in all subgroups, including pts who were LEN refractory and anti-CD38 exposed/refractory. In LEN-refractory pts, BPd treatment led to almost a 3-fold median PFS2 improvement vs PVd (41.7 vs 15.0 mo). A total of 56/155 pts (36%) in the BPd arm and 93/147 (63%) in the PVd arm received any first subsequent therapy (FST) at data cutoff. Across both arms, 36% of pts received steroids, 28% received anti-CD38 therapies (>50% of pts with any subsequent therapy in each arm), and 23% received proteasome inhibitors as FST. A total of 21 pts (7%) received novel therapies (BPd, n=6 [4%]; PVd, n=15 [10%]) as FST, including BCMA-targeted bispecific antibodies (bsAbs), non-BCMA bsAbs, CELMoDs, venetoclax, and belamaf. Improved median PFS2 was observed in patients who had novel therapies as FST (n=21) vs non-novel agents (n=128) (26.0 vs 20.1 mo; HR, 0.61; 95% CI, 0.34-1.09). Conclusions: BCMA-directed therapy, BPd, resulted in improved PFS2 outcomes vs PVd, demonstrating sustained clinical benefit beyond initial belamaf therapy. This benefit was seen regardless of prior treatment, with LEN-refractory pts experiencing almost a 3-fold PFS2 benefit, and despite a higher proportion of pts receiving novel therapies as FST in the PVd arm. PFS2 benefit with high use of subsequent anti-CD38 agents supports sequencing of belamaf combinations early in the treatment paradigm prior to anti-CD38 agents.