Belantamab Mafodotin Combo Sustains MRD Negativity/PFS in Multiple Myeloma

Long-term results from the phase 3 DREAMM-8 trial (NCT04484623) showed that belantamab mafodotin-blmf (Blenrep) plus pomalidomide (Pomalyst) and dexamethasone (BPd) improved minimal residual disease (MRD) negativity and progression-free survival (PFS) in relapsed/refractory multiple myeloma following 1 prior line of therapy, including lenalidomide. These results were shared at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.

Among patients who received treatment with BPd, the overall response rate (ORR) was 76% (95% CI, 68.6%-82.6%) compared with 72% (95% CI, 64.1%-79.2%) among patients who received treatment with bortezomib (Velcade) plus pomalidomide and dexamethasone (PVd); the complete response (CR) or better rate was 43% (95% CI, 35.3%-51.4%) vs 17% (95% CI, 11.3%-24.1%), respectively, and the very good partial response (VGPR) rate was 63% (95% CI, 55.1%-70.8%) vs 39% (95% CI, 30.9%-47.2%).

The VGPR or better-based MRD-negativity rate, defined as 10^-5, was 35% (95% CI, 28.0%-43.6%) with BPd and 7% (95% CI, 3.8%-13.0%) with PVd in the intention-to-treat (ITT) population; in patients with a VGPR or better through post-hoc analyses, it was 56% vs 19%, respectively. The CR or better-based MRD negativity rates were 28% (95% CI, 20.9%-35.5%) with BPd and 6% (95% CI, 2.8%-11.3%) with PVd in the ITT population; in patients with a CR or better, the rates were 64% vs 36%.

The CR or better-based MRD negativity sustained for at least 12 months rate was 15% (95% CI, 10.2%-22.2%) with BPd vs 3% (95% CI, 0.7%-6.8%) with PVd; notably, among the patients with CR or better-based MRD negativity, 56% of the BPd arm and 44% of the PVd arm sustained MRD negativity for 12 or more months.

The median duration of response (DOR) was not reached (NR; 95% CI, 29.5-NR) with BPd vs 16.4 months (95% CI, 11.1-22.5) with PVd, and the 24-month DOR rates were 65% (95% CI, 55%-73%) vs 40% (95% CI, 29%-50%), respectively.

The median PFS was 32.6 months (95% CI, 21.1-NR) with BPd vs 12.5 months (95% CI, 9.1-17.6) with PVd (HR, 0.49; 95% CI, 0.36-0.67); the 24-month PFS rates were 55% (95% CI, 46%-63%) and 31% (95% CI, 22%-39%), respectively. The median time from randomization to disease progression after initiation of new antimyeloma therapy or death from any cause (PFS2) was 47.1 months (95% CI, 28.4-NR) compared with 21.7 months (95% CI, 13.8-28.6), respectively (HR, 0.52; 95% CI, 0.38-0.70); the 24-month PFS2 rates were 61% (95% CI, 53%-69%) and 47% (95% CI, 39%-55%), respectively.

“Long-term follow-up from the DREAMM-8 trial demonstrated that BPd maintained superiority over PVd across all efficacy end points, including PFS, MRD negativity, sustained MRD negativity, and DOR,” wrote lead study author Suzanne Trudel, MSc, MD, a clinical scientist in the Department of Medical Oncology and Hematology, Princess Margaret Cancer Center in Toronto, Ontario, Canada. “Importantly, benefit was maintained following subsequent antimyeloma.”

A total of 302 patients were randomly assigned 1:1 to the BPd arm or the PVd arm. In the BPd arm, patients received intravenous belantamab mafodotin at 2.5 mg/kg in cycle 1, then 1.9 mg/kg every 4 weeks from cycle 2 onward, pomalidomide at 4 mg orally on days 1 to 21, and dexamethasone at 40 mg on days 1, 8, 15, and 22 of each 28-day cycle. In the PVd arm, treatment was subcutaneous bortezomib at 1.3 mg/m² on days 1, 4, 8, and 11 of cycles 1 to 8, pomalidomide at 4 mg orally on days 1 to 14 of 21-day cycles, and dexamethasone at 20 mg on the day of and the day after bortezomib.

Eligible patients were 18 years or older with multiple myeloma, had received at least 1 prior line of therapy, including lenalidomide, had documented progressive disease during or after the most recent therapy, and had no prior receipt of anti-BCMA therapy or pomalidomide, and no disease refractory to or intolerant of bortezomib.

A total of 53% of patients had received 1 prior line of therapy, 34% had received 2 or 3 prior lines, and 14% had received at least 4. Anti-CD38 antibodies were received by 25% of the BPd arm and 29% of the PVd arm, and all patients received prior lenalidomide. Triple-class exposed status was noted in 22% of the BPd arm and 27% of the PVd arm.

Patients who achieved a VGPR or better were tested for MRD negativity by next-generation sequencing with a sensitivity of 10^-5.

The primary end point of the trial was PFS assessed by independent review committee. Key secondary end points were overall survival, MRD negativity, and DOR; other secondary end points included ORR, VGPR or better rate, PFS2, adverse events (AEs), and health-related quality of life.

Regarding safety, any AE occurred in more than 99% of the BPd arm and 97% of the PVd arm, and any grade 3 or 4 AE occurred in 91% and 74%; AEs related to study treatment occurred in 96% and 83%. AEs led to treatment discontinuation, dose reduction, and dose interruption/delay in 22%, 63%, and 91% of the BPd arm, and 14%, 61%, and 76% of the PVd arm.

“Collectively, findings support BPd as a new outpatient and off-the-shelf BCMA treatment as standard of care in multiple myeloma at first relapse,” concluded Trudel.

Reference

Trudel S, Beksac M, Pour L, et al. Deep responses and durable outcomes in patients treated with belantamab mafodotin plus pomalidomide and dexamethasone from long-term follow-up of the phase 3 DREAMM-8 study. Blood. 2025;146(suppl_1):2264. doi:10.1182/blood-2025-2264