Long-term outcomes with sustained minimal residual disease (MRD) negativity in belantamab mafodotin–treated patients (pts) with relapsed/refractory multiple myeloma (RRMM): An update from DREAMM-8.

Abstract

7515 Background: B-cell maturation antigen (BCMA)–directed therapies have changed the RRMM treatment landscape. In the phase 3 DREAMM-8 trial (NCT04484623), BCMA-directed antibody-drug conjugate (ADC) belantamab mafodotin + pomalidomide and dexamethasone (BPd) demonstrated significant progression-free survival (PFS) benefit and higher rates of complete response (CR)–based MRD negativity vs triplet pomalidomide, bortezomib, dexamethasone (PVd) in pts with RRMM and ≥1 prior line of therapy (LOT). As MRD negativity predicts improved survival in MM, this long-term, postbaseline update describes clinical outcomes and characteristics of pts with sustained MRD negativity. Methods: Pts with ≥1 prior LOT including lenalidomide were randomized 1:1 to BPd or PVd. The primary endpoint was PFS (independent review committee assessed); PFS2 was investigator assessed. CR-based sustained MRD negativity (≥12 mo) was an exploratory endpoint. Pts with ≥ CR were tested for MRD negativity by next-generation sequencing (10 −5 sensitivity). Results: At data cutoff (7/7/2025), with median follow-up of 35.8 mo overall, the intention-to-treat population of BPd (n=155) vs PVd (n=147) was >4× more likely to achieve ≥ CR + MRD negativity (27.7% vs 6.1%) and sustained MRD negativity (15.5% vs 2.7%). In pts with ≥ CR (BPd, n = 67; PVd, n = 25), rates of MRD negativity were also higher with BPd vs PVd (64.2% vs 36.0%), as were rates of sustained MRD negativity (55.8% vs 44.4%) among all ≥ CR + MRD negative pts. Pts with sustained MRD negativity had durable PFS in both arms; 1 of 24 and 0 of 4 pts experienced PFS events with BPd and PVd, respectively. In pts without sustained MRD negativity, median PFS was 21.1 mo with BPd (HR vs sustained MRD negative, 0.04; 95% CI, 0.01-0.32) and 10.2 mo with PVd (HR vs sustained MRD negative, not estimable [NE]). Sustained MRD negativity was also associated with durable PFS2 in both arms; 2 of 25 and 0 of 4 pts experienced PFS2 events with BPd and PVd, respectively. In pts without sustained MRD negativity, median PFS2 was 20.2 mo with BPd (HR vs sustained MRD negative, 0.08; 95% CI, 0.02-0.33) and 9.3 mo with PVd (HR vs sustained MRD negative, NE). Findings were similar in pts with vs without ≥ CR + MRD negativity. Of BPd-treated pts, those with MRD negativity (n=43) received 1-3 prior LOT, of which most (74.4%) had 1. MRD-positive pts (n=112) received up to 6 prior LOT, of which 44.6% received 1 and 17.0% received >3. Almost 40% of pts with CR-based MRD negativity had high-risk cytogenetics. Conclusions: Pts receiving BPd vs PVd were >4× more likely to achieve sustained MRD negativity, which was associated with improved PFS and PFS2. MRD negative vs positive pts in the BPd arm more often had 1 prior LOT. These findings further support BPd, a BCMA-directed ADC regimen, in earlier LOTs for RRMM, including in pts with high-risk cytogenetics. Clinical trial information: NCT04484623 .