KEY TAKEAWAYS
- The DREAMM 8 phase 3 trial aimed to investigate the efficacy and safety of BPd compared to standard of care PVd in patients with R/R MM.
- The primary endpoint was to determine PFS.
- Researchers concluded that BPd offers superior PFS, deeper responses, favorable OS trend and manageable safety in patients with R/R MM.
Use of triplet/quadruplet therapies in the 1L treatment setting for multiple myeloma (MM) raises the need for novel combinations at first relapse, which belantamab mafodotin (belamaf) combinations may address. In DREAMM-7, belamaf plus bortezomib and dexamethasone (BVd) significantly improved progression-free survival (PFS) and showed a strong trend in improved overall survival (OS) vs daratumumab-Vd in patients (pts) with ≥1 prior therapy.
They reported results from DREAMM-8 (NCT04484623), which tested a different belamaf combination (belamaf plus pomalidomide and dexamethasone [BPd]) and met its primary endpoint of independent review committee–assessed PFS at a prespecified interim analysis.
Dr. Meletios Dimopoulos and the team aimed to evaluate the efficacy and safety of BPd vs those of standard of care (pomalidomide plus bortezomib and dexamethasone [PVd]) in pts with relapsed/refractory MM (RRMM) previously treated with lenalidomide.
They performed an inclusive analysis in DREAMM-8, a phase 3, open-label, randomized, multicenter trial comparing BPd versus PVd in patients with RRMM who had received ≥1 prior line of therapy (LOT), including lenalidomide. Patients were randomized 1: 1 to BPd (28-day cycles)—belamaf 2.5 mg/kg IV (day 1, cycle 1), 1.9 mg/kg (day 1, cycle 2+) + pomalidomide 4 mg (days 1-21, all cycles) + dexamethasone 40 mg (day 1, weekly, all cycles) or PVd (21-day cycles)—pomalidomide 4 mg (days 1-14, all cycles) + bortezomib 1.3 mg/m2 SC (days 1, 4, 8, and 11 [cycles 1-8]; days 1 and 8 [cycles 9+]) + dexamethasone 20 mg (day of and 1 day after bortezomib dose).
At data cutoff (29 January 2024), 155 patients were randomized to BPd (median [range] LOT, 1 [1-6]) and 147 to PVd (median [range] LOT, 1 [1-9]); 25% and 29% of patients had prior anti-CD38 antibody, respectively. With a median (range) follow-up of 21.78 months (0.03-39.23 months), median PFS (95% CI) was not reached (NR; 20.6 months to NR) with BPd versus 12.7 months (9.1-18.5 months) with PVd (hazard ratio [HR], 0.52; 95% CI, 0.37-0.73; P < 0.001); 12-month PFS rate (95% CI) was 71% (63%-78%) with BPd versus 51% (42%-60%) with PVd.
ORR (95% CI) was 77% (70.0%-83.7%) with BPd versus 72% (64.1%-79.2%) with PVd; rate of complete response or better (95% CI) was 40% (32.2%-48.2%) with BPd versus 16% (10.7%-23.3%) with PVd. Median DOR (95% CI) was not reached (24.9 months to NR) with BPd versus 17.5 months (12.1-26.4 months) with PVd. A positive trend favoring BPd was seen for OS (HR, 0.77; 95% CI, 0.53-1.14); follow-up for OS is ongoing. In the safety analysis set, adverse events (AEs) were observed in the BPd arm (N = 150; any grade, >99%; grade 3/4, 91%) and PVd arm (N = 145; 96%; 73%).
In the BPd arm, 89% of patients had ocular AEs (CTCAE) (grade 3/4, 43%) versus 30% (grade 3/4, 2%) in the PVd arm; serious AEs (SAEs) were reported in 63% and 45% of patients, respectively, and fatal SAEs were reported in 11% of patients in both arms. In total, 15% and 12% of patients 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.
The trial concluded that BPd demonstrated a statistically significant and clinically meaningful PFS benefit over PVd in RRMM with >1 prior LOT. BPd also resulted in deeper and more durable responses, exhibited a favorable trend in OS, and maintained a manageable safety profile.
The trial was sponsored by the GlaxoSmithKline.
Clinical Trial: https://clinicaltrials.gov/study/NCT04484623
Dimopoulos M.A., Beksac M, Pour L, et al. (2024). “RESULTS FROM THE RANDOMIZED PHASE 3 DREAMM-8 STUDY OFBELANTAMAB MAFODOTIN PLUS POMALIDOMIDE AND DEXAMETHASONE VSPOMALIDOMIDE PLUS BORTEZOMIB AND DEXAMETHASONE INREPALPSED/REFRACTORY MULTIPLE MYELOMA.” Presented at EHA 2024.
