The combination of belantamab mafodotin, pomalidomide, and dexamethasone showed a median PFS of 32.6 months in relapsed/refractory multiple myeloma.
Belantamab mafodotin-blmf (Blenrep) plus pomalidomide (Pomalyst) and dexamethasone (BPd) produced improvements in progression-free survival (PFS) and minimal residual disease (MRD) negativity in patients diagnosed with relapsed/refractory multiple myeloma after 1 prior line of therapy, including lenalidomide (Revlimid), according to data from the DREAMM-8 study (NCT04484623) presented at the
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.
