Key Clinical Summary:

• Population and Design: Phase 3 DREAMM-8 enrolled R/R MM patients with ≥ 1 prior therapy, all lenalidomide-exposed and many lenalidomide- or anti-CD38–refractory. Patients were randomized to belantamab mafodotin in combination with pomalidomide and dexamethasone (BPd) or standard regimen of pomalidomide, bortezomib, and dexamethasone (PVd) and followed for a median of 35.8 months. Primary end point was PFS; key secondary end points included response rates, MRD negativity, DOR, PFS2, and safety.
• Findings: BPd significantly prolonged PFS (32.6 vs 12.5 months; HR 0.49) compared with PVd. Depth of response was greater with BPd, with ≥CR rates of 43% vs 17% and nearly 5× higher MRD negativity. Responses were more durable (median DOR not reached vs 16.4 months; 65% vs 40% at 24 months). PFS2 also favored BPd, and the safety profile remained consistent, with higher grade 3/4 AEs but no new signals.
• Clinical Relevance: BPd offers a strong efficacy advantage—including deeper, more durable responses—in a population with substantial treatment refractoriness. The >30-month median PFS and sustained benefit after next therapy support BPd as a potential new standard of care at first relapse. As an outpatient regimen with manageable toxicity, BPd provides an accessible option for early-relapse RRMM.

In the setting of relapsed or refractory (R/R) multiple myeloma (MM), where most patients have been exposed or become refractory to lenalidomide and increasingly to anti-CD38 monoclonal antibodies, treatment options with durable outcomes remain limited. Updated results from the phase 3 DREAMM-8 trial now provide compelling long-term evidence supporting belantamab mafodotin in combination with pomalidomide and dexamethasone (BPd) as a potential new standard of care.

DREAMM-8 randomized 302 patients with R/R MM who had received at least 1 prior therapy, including lenalidomide, to either BPd or the standard regimen of pomalidomide, bortezomib, and dexamethasone (PVd). With extended follow-up of 35.8 months, BPd continued to demonstrate a robust and clinically meaningful progression-free survival benefit. Median PFS more than doubled with BPd—32.6 months versus 12.5 months with PVd—corresponding to a hazard ratio (HR) of 0.49.

The depth and durability of responses also improved substantially with BPd. Complete responses or better were achieved by 43% of BPd-treated patients, compared with 17% in the PVd arm. MRD negativity at the ≥CR level occurred nearly five times more frequently with BPd, and sustained MRD negativity for at least 12 months was achieved by 15% of patients, versus just 3% with PVd. The median duration of response was not reached with BPd, and two-thirds of responders maintained benefit for at least 24 months, compared with 40% in the comparator arm. Importantly, PFS2 analysis showed that the advantage of BPd persisted even after initiation of subsequent therapy.

Safety findings remained consistent with the primary analysis. Although grade 3/4 adverse events and treatment discontinuations were more common with BPd, no new safety signals emerged, and the regimen remained feasible in the outpatient setting.

“After extended follow-up of the DREAMM-8 trial, BPd led to a substantial increase in response depth and durability vs PVd in a population of [patients]with R/R MM, most of whom had lenalidomide-refractory disease and a quarter of whom had disease refractory to anti-CD38 monoclonal antibodies,” explained Trudel et al. 

 “The updated safety profile of BPd was broadly consistent with the primary analysis. BPd resulted in a median PFS of >30 months and a maintained PFS benefit following subsequent antimyeloma therapy; as a combination that can be easily administered in the outpatient setting, these results support BPd as a potential new standard of care in RRMM,” they concluded. 

Source:

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. Dec 6-9, 2025; Orlando, FL. Abstract: 2264