DREAMM-8 Produces Positive Topline Results in Relapsed/Refractory Multiple Myeloma

GSK, the manufacturer of the antibody-drug conjugate belantamab mafodotin-blmf (Blenrep), has announced positive topline findings from the phase 3 DREAMM-8 trial (NCT04484623), which is evaluating belantamab mafodotin plus pomalidomide (Pomalyst) and dexamethasone vs standard of care bortezomib (Velcade) plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma. The study met its primary end point of progression-free survival (PFS) at a prespecified interim analysis and was unblinded early as recommended by an independent data monitoring committee.¹

Additionally, at the time of the analysis, a positive trend for overall survival (OS) was observed in the investigational arm vs the control arm; the study continues to follow patients for OS.

“The results seen in both [the phase 3] DREAMM-7 [NCT04246047] and DREAMM-8 [trials] provide strong clinical evidence of the robust efficacy shown with belantamab mafodotin in use with standard of care combinations,” Hesham Abdullah, MD, MSc, senior vice president, global head oncology, R&D, GSK, said in a press release. “We now look forward to discussing these data with regulators. If approved, we believe these combinations have the potential to redefine the treatment of relapsed or refractory multiple myeloma and advance the standard of care. This is exciting news for patients given the high unmet medical need for both efficacious and easily administered therapies with differing mechanisms of action.”

DREAMM-8 is a multicenter, open-label study comparing belantamab mafodotin plus pomalidomide and dexamethasone vs bortezomib plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who previously received at least 1 line of treatment for multiple myeloma, including a lenalidomide (Revlimid)-containing regimen. To be eligible for the study, patients must have an ECOG performance status of 2 or less, have experienced progression during or after their most recent multiple myeloma therapy, have undergone autologous stem cell transplant or are transplant ineligible, and have adequate organ function.²

After enrollment, approximately 450 patients will be randomly assigned 1:1 to arm A or arm B. In arm A, patients were treated with intravenous belantamab mafodotin 2.5 mg/kg every 4 weeks on day 1 of cycle 1 followed by belantamab mafodotin 1.9 mg/kg on day 1 of cycle 2 and beyond plus pomalidomide 4 mg on days 1 through 21 with dexamethasone 40 mg on days 1, 8, 15, and 22 of all cycles. In arm B, patients received pomalidomide 4 mg every 3 weeks on days 1 through 14 of each 21-day cycle, subcutaneous bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 in cycles 1 through 8, and days 1 and 8 in cycle 9 and beyond; dexamethasone 20 mg was given on the day of and the day after bortezomib. Patients will be stratified by number of prior lines of treatment, prior exposure to bortezomib, and International Staging System status.³

The primary end point is PFS. Secondary end points include OS, overall response rates, minimal residual disease negativity rate per next-generation sequencing, and safety.²

Previously, findings from DREAMM-7 showed that belantamab mafodotin in combination with bortezomib plus dexamethasone (n = 243) nearly tripled median PFS compared with daratumumab (Darzalex) plus bortezomib and dexamethasone (n = 251). At a median follow-up of 28.2 months, the median PFS was 36.6 months (95% CI, 28.4-not reached) vs 13.4 months (95% CI, 11.1-17.5), respectively (HR, 0.41; 95% CI, 0.31-0.53; P < .00001). Notably, the PFS benefit was observed in all prespecified subgroups, including among patients who were refractory to lenalidomide and those with high-risk cytogenetics.⁴

In the press release, GSK noted that detailed findings from DREAMM-8 will be presented at a future medical meeting and provided to regulatory authorities.¹

References

1. GSK announces positive results from DREAMM-8 phase III trial for Blenrep versus standard of care combination in relapsed/refractory multiple myeloma. News release. GSK. March 7, 2024. Accessed March 7, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-positive-results-from-dreamm-8-phase-iii-trial-for-blenrep-versus-standard-of-care-combination-in-relapsedrefractory-multiple-myeloma/
2. Belantamab mafodotin plus pomalidomide and dexamethasone (Pd) versus bortezomib plus Pd in relapsed/​refractory multiple myeloma (DREAMM 8). ClinicalTrials.gov. Updated November 2, 2023. Accessed March 7, 2024. https://clinicaltrials.gov/study/NCT04484623
3. Trudel S, Davis R, Lewis NM, et al. DREAMM-8: a phase III study of the efficacy and safety of belantamab mafodotin with pomalidomide and dexamethasone (B-Pd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in patients with relapsed/refractory multiple myeloma (RRMM). Blood. 2020;136(suppl 1):4. doi:10.1182/blood-2020-139785
4. DREAMM-7 phase III trial shows Blenrep combination nearly tripled median progression-free survival versus standard of care combination in patients with relapsed/refractory multiple myeloma. News release. GSK. February 5, 2024. Accessed March 7, 2024. https://www.gsk.com/en-gb/media/press-releases/dreamm-7-phase-iii-trial-shows-pfs-improvement-and-strong-os-trend-for-blenrep-combo-versus-soc-combo-in-multiple-myeloma/