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).

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 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.