OA – 62: Results from the randomized phase 3 DREAMM-8 study of belantamab mafodotin, pomalidomide, dexamethasone vs pomalidomide plus bortezomib, dexamethasone (PVd) in relapsed/refractory multiple myeloma
Professor of Medicine Princess Margaret Cancer Centre, Toronto, ON, Canada Toronto, Ontario, Canada
Introduction: Use of triplet/quadruplet therapies as 1L treatment for multiple myeloma (MM) raises the need for novel combinations at first relapse. In DREAMM-7, belamaf plus bortezomib and dexamethasone (BVd) led to a significant improvement in progression-free survival (PFS) and a strong trend in improved overall survival (OS) vs daratumumab-Vd in patients (pts) with ≥1 prior line of therapy (LOT). We report results from DREAMM-8 (NCT04484623), which met its primary endpoint of independent review committee–assessed PFS at a prespecified interim analysis.
Methods: DREAMM-8 is a phase 3, open-label, randomized, multicenter trial evaluating BPd vs PVd in pts with RRMM who received ≥1 prior LOT including lenalidomide. Pts were randomized 1:1 to BPd (28-day [D] cycles)—belamaf 2.5 mg/kg IV (D 1, cycle [C] 1), then 1.9 mg/kg (D1, C2+) + pomalidomide 4 mg (D 1-21, all C) + dexamethasone 40 mg (D1, QW, all C) vs PVd (21-D C)—pomalidomide 4 mg (D 1-14, all C) + bortezomib 1.3 mg/m2 SC (D 1, 4, 8, and 11 [Cs 1-8]; days 1 and 8 [C 9+]) + dexamethasone 20 mg (D of and 1 D after bortezomib dose).
Results: At data cutoff (29 Jan 2024), 155 pts were randomized to BPd (median [range] LOT, 1 [1-6]) and 147 to PVd (median [range] LOT, 1 [1-9]); 25% and 29% of pts had prior anti-CD38 antibody, respectively. With a median (range) follow-up of 21.78 mo (0.03-39.23), median PFS (95% CI) was NR (20.6-NR) with BPd vs 12.7 mo (9.1-18.5) with PVd (HR, 0.52; 95% CI, 0.37-0.73; P< 0.001); 12-mo PFS rate (95% CI) was 71% (63-78) with BPd vs 51% (42-60) with PVd. ORR (95% CI) was 77% (70.0-83.7) with BPd vs 72% (64.1-79.2) with PVd; rate of CR or better (95% CI) was 40% (32.2-48.2) with BPd vs 16% (10.7-23.3) with PVd. Median duration of response (95% CI) was NR (24.9-NR) with BPd vs 17.5 mo (12.1-26.4) with PVd. A positive trend favoring BPd was seen for OS (HR, 0.77; 95% CI, 0.53-1.14); follow-up is ongoing. In the safety analysis set, adverse events (AEs) were observed in the BPd (n=150; [any grade, >99%; grade 3/4, 91%]) and PVd arms (n=145; [96%; 73%]). In the BPd arm, 89% of pts had ocular AEs (CTCAE) (grade 3/4, 43%) vs 30% (grade 3/4, 2%) in the PVd arm; serious AEs (SAEs) were reported in 63% and 45% of pts, respectively; fatal SAEs were reported in 11% of pts in both arms. 15% and 12% of pts discontinued treatment due to AEs in the BPd and PVd arms, respectively. AEs were generally manageable and broadly consistent with the known safety profile of the individual agents. Additional analyses will be presented.
Conclusions: DREAMM-8 demonstrated a statistically significant and clinically meaningful PFS benefit with BPd vs PVd in RRMM with ≥1 prior LOT. BPd led to deeper and more durable responses, showed a favorable OS trend, and had a manageable safety profile.
