Minimal residual disease (MRD) negativity (neg) in patients (pts) with relapsed or refractory multiple myeloma (RRMM) treated with belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide, bortezomib, and dexamethasone (PVd): Analysis from the DREAMM-8 trial.
Authors: Suzanne Trudel, Meral Beksac, Luděk Pour, Sosana Delimpasi, Vladimir I. Vorobyev, Hang Quach, Kihyun Kim, Kazuhito Suzuki, Maria-Victoria Mateos, Jie Ma, Yinjiao Ma, Ianire Garrobo-Calleja, Giulia Fulci, Elisabet Manasanch, Neal Sule, Brandon Kremer, Pralay Mukhopadhyay, Joanna Opalinska, Meletios Athanasios Dimopoulos
Journal: Journal of Clinical Oncology (2025)

7515 Background: In DREAMM-8 (NCT04484623), BPd demonstrated a statistically significant, clinically meaningful benefit to progression-free survival (PFS) vs PVd in pts with RRMM who received ≥1 prior line of treatment including lenalidomide. MRD neg has been shown to be a predictor of PFS and overall survival (OS) in MM. We assessed efficacy outcomes by MRD status. Methods: Ptswere randomized (1:1) to BPd or PVd. The primary endpoint was independent review committee (IRC)–assessed PFS; OS, duration of response, and MRD status determined by next-generation sequencing with 10 −5 sensitivity threshold was assessed in pts with complete response or better (≥CR) every 6 mo until progressive disease. Post hoc subgroup analyses of PFS and OS were conducted based on IRC-assessed response (≥CR or ≥VGPR) and MRD-neg status using Kaplan-Meier method; CIs were estimated using Brookmeyer-Crowley method. Results: 302 pts were randomized to BPd (n=155) or PVd (n=147). As previously reported (median follow-up, 21.8 mo), more pts with BPd had CR-based MRD neg vs PVd (37/155 [24%] vs 7/147 [5%]). A similar trend was seen in pts with ≥VGPR; 50/155 pts (32%) had VGPR-based MRD neg with BPd vs 8/147 (5%) with PVd. In the DREAMM-8 trial, MRD neg was associated with improved efficacy outcomes (Table). Pts with CR-based MRD neg had a lower risk of disease progression or death compared with pts without MRD neg (PFS HR, 0.14; 95% CI, 0.06-0.32; Table); median was NR overall and in each treatment arm (HR [BPd vs PVd], 0.90; 95% CI, 0.10-7.76). MRD neg pts had a lower risk of death (OS HR, 0.18; 95% CI, 0.07-0.49). In all pts who did not have CR-based MRD neg, pooled median PFS was 14.0 mo (95% CI, 11.1-18.6 mo; BPd, 19.6 mo; PVd, 10.2 mo; HR [BPd vs PVd], 0.67; 95% CI, 0.47-0.94), and the pooled 18-mo PFS rate was 46% (95% CI, 39%-52%; BPd, 52%; PVd, 39%). Median OS was NR overall, 33.0 mo (95% CI, 23.7-NR) with BPd and NR with PVd; 18-mo OS rate was 69% (95% CI, 63%-75%; BPd, 72%; PVd, 67%). Conclusions: Consistent with previous reports, MRD neg was associated with a robust benefit in PFS and OS, highlighting the significance of a greater response depth. Pts with BPd achieved a 5-fold improvement in CR-based MRD neg vs PVd (24% vs 5%). Pts who did not achieve CR-based MRD neg had a clinically meaningful benefit in PFS with BPd vs PVd. Clinical trial information: NCT04484623 . MRD neg Non-MRD neg MRD status (≥CR), n Pooled (44) BPd (37) PVd (7) Pooled (258) BPd (118) PVd (140) Median PFS (95% CI), mo NR (NR-NR) NR (NR-NR) NR (NR-NR) 14.0 (11.1-18.6) 19.6 (13.5-NR) 10.2 (8.4-17.1) 18-mo PFS rate (95% CI), % 93 (79-98) 91 (75-97) 100 (100-100) 46 (39-52) 52 (42-62) 39 (30-48) 18-mo OS rate (95% CI), % 93 (80-98) 92 (76-97) 100 (100-100) 69 (63-75) 72 (62-79) 67 (59-74)