GlaxoSmithKline plc has initiated the process to withdraw the United States marketing authorization for belantamab mafodotin-blmf for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior therapies.
GlaxoSmithKline (GSK) plc has initiated the process to withdraw the United States marketing authorization for belantamab mafodotin-blmf (Blenrep) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor (PI), and an immunomodulatory agent.1
The decision to withdraw the US indication for belantamab mafodotin stems from a request from the FDA following the results of the phase 3 DREAMM-3 trial (NCT04162210), which showed that the study did not meet its primary end point of a progression-free survival (PFS) benefit with belantamab mafodotin vs the combination of pomalidomide (Pomalyst) plus low-dose dexamethasone.2
At a median follow-up of 11.5 months for the belantamab mafodotin arm and 10.8 months for pomalidomide plus low-dose dexamethasone arm, patients treated with belantamab mafodotin experienced a median PFS of 11.2 months compared with 7.0 months for pomalidomide plus dexamethasone (HR, 1.03; 95% CI, 0.72-1.47).
GSK announced that patients already enrolled in the Blenrep Risk Evaluation and Mitigation Strategy program will have the option to enroll in a compassionate use program to continue access to treatment.
“We respect the [FDA’s] approach to the accelerated approval regulations and associated process. Multiple myeloma is a challenging disease, with poor outcomes for patients whose disease has become resistant to standard-of-care treatments. We will continue the DREAMM clinical trial program and work with the FDA on a path forward for this important treatment option for patients with multiple myeloma,” Sabine Luik, MD, MBA, chief medical officer of GSK, stated in a news release.
In August 2020, the FDA granted accelerated approval to belantamab mafodotin for the treatment of patients with relapsed/refractory multiple myeloma who have received 4 prior therapies, including an immunomodulatory drug, a PI, and an anti-CD38 antibody.3 The regulatory decision was based on results of the phase 2 DREAMM-2 trial (NCT03525678).
The open-label, randomized DREAMM-3 study investigated the efficacy and safety of belantamab mafodotin monotherapy vs pomalidomide plus dexamethasone in patients at least 18 years old with histologically or cytologically confirmed relapsed/refractory multiple myeloma who had undergone autologous stem cell transplant (ASCT) or were considered transplant ineligible, and had received at least 2 prior lines of anti-myeloma treatments, including at least 2 consecutive cycles of both lenalidomide (Revlimid) and a PI. Patients were required to have documented disease progression on, or within 60 days of, completion of the last treatment or must be non-responsive while on last treatment.4
Patients were required to have an ECOG performance status of 0 to 2, adequate organ function, and resolution of all prior treatment-related toxicities to grade 1 or lower, except for alopecia or grade 2 peripheral neuropathy. For patients who underwent prior ASCT, transplant must have been completed more than 100 days prior to initiating study treatment, and no active infections were permitted.
Enrollment was not permitted for patients with symptomatic amyloidosis, active POEMS syndrome, or active plasma cell leukemia; any systemic anti-myeloma therapy or use of an investigational drug within 14 days or 5 half-lives, whichever was shorter, before the first dose of study treatment; prior treatment with an anti–multiple myeloma monoclonal antibody within 30 days prior to first study treatment; prior BCMA-targeted therapy or prior pomalidomide treatment; prior allogeneic stem cell transplant; or any major surgery within 4 weeks of the start of study treatment.
DREAMM-3 randomly assigned patients 2:1 to 2.5 mg/kg of belantamab mafodotin once every 3 weeks, or pomalidomide administered daily on days 1 to 21 of each 28-day cycle plus dexamethasone given once weekly on days 1, 8, 15, and 22 of each cycle.
Along with the primary end point of PFS, secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DOR), assessment of minimal residual disease, and safety.
Additional data from the phase 3 trial showed belantamab mafodotin generated an ORR of 41% compared with 36% for pomalidomide plus dexamethasone. Twenty-five percent of patients in the belantamab mafodotin arm achieved a very good partial response or better, vs 8% of those in the experimental arm. The DOR was not yet reached (95% CI, 17.9–not estimable [NE]) for belantamab mafodotin vs 8.5 months (95% CI, 7.6-NE) for pomalidomide plus low-dose dexamethasone. The 12-month DOR rates were 76.8% and 48.4% for belantamab mafodotin and pomalidomide plus low-dose dexamethasone, respectively.
OS data reached 37.5% overall maturity at the time of data cutoff. The median OS was 21.2 months for belantamab mafodotin compared with 21.1 months for pomalidomide plus dexamethasone (HR, 1.14; 95% CI, 0.77-1.68).
Regarding safety, findings for belantamab mafodotin were similar to the known safety profile of the agent, with no new safety signals were identified. Rates of grade 3 keratopathy were consistent with previously reported data.
Belantamab mafodotin remains under investigation in multiple phase 3 trials exploring the agent’s efficacy and safety in combination with other agents. The DREAMM-7 trial (NCT04246047) is investigating belantamab mafodotin plus bortezomib (Velcade) and dexamethasone vs daratumumab (Darzalex) plus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma who received at least 1 prior multiple myeloma therapy.5
The DREAMM-8 trial (NCT04484623) in examining belantamab mafodotin plus pomalidomide and dexamethasone vs bortezomib plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who had at least 1 prior line of multiple myeloma therapy including a lenalidomide-containing regimen.6