Belantamab mafodotin plus bortezomib and dexamethasone significantly improved progression-free survival compared with daratumumab plus B-Vd in the second-line treatment of patients with relapsed or refractory multiple myeloma, meeting the primary end point of the phase 3 DREAMM-7 trial.
Belantamab mafodotin-blmf (Blenrep) plus bortezomib (Velcade) and dexamethasone (B-Vd) significantly improved progression-free survival (PFS) compared with daratumumab (Darzalex) plus B-Vd (D-Vd) in the second-line treatment of patients with relapsed or refractory multiple myeloma, meeting the primary end point of the phase 3 DREAMM-7 trial (NCT04246047).1
At the time of the planned interim efficacy analysis, a clinically meaningful trend in overall survival (OS) was also observed with the belantamab mafodotin regimen (nominal P < .0005). Investigators will continue to follow up for OS, according to GlaxoSmithKline. The safety regimen of the combination was found to be consistent with what has previously been reported with each individual drug.
“Patients with multiple myeloma need treatment options after first relapse that are efficacious, readily accessible and have novel mechanisms of action,” Hesham Abdullah, senior vice president and global head of Oncology, R&D at GlaxoSmithKline, stated in a press release. “We are particularly encouraged by the potential for belantamab mafodotin when combined with BorDex to address high unmet need in relapsed/refractory multiple myeloma, given the head-to-head comparison with the daratumumab-based, standard-of-care regimen.”
The multicenter, open-label phase 3 trial enrolled patients with a confirmed diagnosis of multiple myeloma as defined by International Myeloma Working Group criteria who previously received at least 1 line of therapy and progressed during or following their most recent treatment.2,3 Patients needed to be at least 18 years of age, have an ECOG performance status ranging from 0 to 2, and acceptable organ function. All previous treatment-related adverse effects (AEs) must have resolved to grade 1 or less severity at the time of enrollment with the exception of alopecia.
Those who were intolerant or refractory to daratumumab, other anti-CD38 agents, or bortezomib were excluded. Patients could not have previously received anti-BCMA therapy or have undergone allogeneic stem cell transplant. Other exclusion criteria included having corneal epithelial disease or ongoing peripheral neuropathy or neuropathic pain that was grade 2 or higher.
Study participants (n = 494) were randomly assigned 1:1 to receive belantamab mafodotin plus B-Vd or daratumumab plus D-Vd.1,2 Belantamab mafodotin was given intravenously, at a dose of 2.5 mg/kg every 3 weeks.1 Treatment continued until disease progression, intolerable toxicity, withdrawn consent, death, or study completion.2
In addition to PFS serving as the trial’s primary end point, secondary end points include complete response rate, objective response rate, duration of response, time to response, time to progression, OS, PFS on subsequent line of therapy, minimal residual disease negativity rate, AEs or serious AEs, antidrug antibodies, health-related quality of life, patient-reported outcomes, pharmacokinetics, and ocular data.
Data from the interim analysis will be shared at an upcoming medical meeting and discussed with health authorities, according to GlaxoSmithKline.1
In November 2022, the pharmaceutical company initiated the process to withdraw the US marketing authorization for belantamab mafodotin in adult patients with relapsed/refractory multiple myeloma who previously received at least 4 therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.4 The decision to withdraw the indication was based on a FDA request following data from the phase 3 DREAMM-3 trial (NCT04162210), which indicated that belantamab mafodotin did not improve PFS over pomalidomide (Pomalyst) and low-dose dexamethasone.5
Moreover, in September 2023, the European Medicines Agency’s Committee for Medicinal Produces for Human Use recommended against the renewal of the conditional marketing authorization for belantamab mafodotin for patients with relapsed/refractory multiple myeloma who had received at least 4 prior therapies.6 Comparative data for the agent had not been available at the time that the European Commission approved the agent in August 2020,7 and DREAMM-3 did not meet its primary end point.