medwireNews: The combination of belantamab mafodotin (belamaf), pomalidomide plus dexamethasone (BPd) offers a significant progression-free survival (PFS) benefit in people with relapsed or refractory multiple myeloma, indicate results from DREAMM-8.
Treatment with BPd almost halved the risk for progression or death compared with the control regimen of pomalidomide, bortezomib, and dexamethasone (PVd), investigator Suzanne Trudel (Princess Margaret Cancer Centre, Toronto, Ontario, Canada) told delegates of the 2024 ASCO Annual Meeting, held in Chicago, Illinois, USA.
“The safety and tolerability of BPd was consistent with the known safety profile of the individual agents,” she noted, adding that “while ocular events were frequent [with BPd], they were generally reversible, manageable with dose modification, and led to a low treatment discontinuation.”
The presenter explained that belamaf “is a first-in-class antibody–drug conjugate that targets BCMA,” and in the DREAMM-7 study, adding belamaf rather than daratumumab to bortezomib plus dexamethasone significantly improved the outcomes of patients with previously treated multiple myeloma.
For the DREAMM-8 phase 3 trial, the team recruited 302 patients with relapsed or refractory disease who had received at least one prior line of therapy that included lenalidomide. The participants were randomly assigned to receive either:
- intravenous belamaf at a dose of 2.5 mg/kg on day 1 of the first 28-day cycle and then 1.9 mg/kg from cycle 2 onward plus pomalidomide 4 mg on days 1–21 and dexamethasone 40 mg on days 1, 8, 15, and 22; or
- bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of the first eight 21-day cycles and then on days 1 and 8 plus pomalidomide 4 mg on days 1–14 and dexamethasone 20 mg on the day that bortezomib was given and the next day.
Analysis at a median follow-up of 21.8 months revealed a significant PFS benefit of BPd versus PVd, with the median unreached and 12.7 months, respectively, corresponding to a hazard ratio for progression or death of 0.52 in favor of the belamaf-based regimen.
The PFS rate at 12 months was 71% in the BPd treatment arm and 51% in the PVd arm.
Trudel highlighted that although the objective response rates in the groups were similar, at 77% and 72%, respectively, the belamaf combination was associated with “deeper responses,” such that the proportion of patients achieving a complete response or better “was more than double” that seen with PVd (40 vs 16%). And the median duration of response was longer, at unreached and 17.5 months, respectively.
Moving onto the safety data, the investigator noted that although the incidence of grade 3–4 adverse events (AEs) and that of serious AEs was numerically higher in the BPd arm, the median duration of treatment was also longer, and after adjustment for treatment exposure, the rates “were similar or lower” in the BPd group.
Ocular events are known to occur with belamaf, she explained, and these were managed by dose interruptions in 83% of patients and by dose reductions in 59%. The rate of discontinuation due to ocular AEs was low, however, at 9%, Trudel pointed out.
In conclusion, Trudel said that “these results, along with those of DREAMM-7, suggest that belamaf combinations can be a new standard of care at first relapse or later due to robust efficacy, manageable safety, and ease of administration.”
The trial results also appear simultaneously in The New England Journal of Medicine.
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2024 ASCO Annual Meeting; Chicago, Illinois, USA: 31 May–4 June
N Engl J Med 2024; doi:10.1056/NEJMoa2403407
