The European Commission has approved belantamab mafodotin-blmf for the treatment of adult patients with multiple myeloma who have received at least 4 previous therapies, whose disease is refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 anti-CD38 monoclonal antibody, and who have progressed on their last therapy.
The European Commission has approved belantamab mafodotin-blmf (Blenrep) for the treatment of adult patients with multiple myeloma who have received at least 4 previous therapies, whose disease is refractory to at least 1 proteasome inhibitor (PI), 1 immunomodulatory agent (IMiD), and 1 anti-CD38 monoclonal antibody, and who have progressed on their last therapy.1
The regulatory decision was based on data from the phase 3 DREAMM-2 study, including 13 months of follow-up, which showed that the antibody-drug conjugate (ADC) resulted in an overall response rate (ORR) of 32% in patients with relapsed/refractory multiple myeloma who had been given the agent at the recommended dose of 2.5 mg/kg every 3 weeks. The median duration of response (DOR) with belantamab mafodotin was 11 months. Moreover, the median overall survival with the agent was 13.7 months in this population.
“The approval of [belantamab mafodotin] marks an important step forward for patients in Europe where nearly 50,000 new cases of multiple myeloma are diagnosed each year,” Hal Barron, MD, chief scientific officer and president of R&D at GlaxoSmithKline (GSK), stated in a press release. “Unfortunately, most of these patients will relapse or stop responding to current therapies so I am pleased that today’s news will give patients with limited treatment options access to the first approved anti-BCMA therapy.”
In the open-label, dual-arm, phase 2 trial, investigators enrolled a total of 196 patients with relapsed/refractory myeloma to the intent-to-treat population between June 18, 2018 and January 2, 2019. Participants were then randomized 1:1 to receive intravenous belantamab mafodotin at a dose of 2.5 mg/kg (n = 97) or a dose of 3.4 mg/kg (n = 99) every 3 weeks until progressive disease or intolerable toxicity.
To be eligible for participation, patients had to have an ECOG performance status ranging from 0 to 2, have progressed on 3 or more lines of therapy, been refractory to a PI and an IMiD, and been refractory and/or intolerant to a CD38-directed monoclonal antibody.
Patient characteristics were determined to be well balanced between the 2 arms.2 In the 2.5-mg/kg cohort, the median age of patients was 65 years, 53% were male, and 42% had high-risk cytogenetics. Participants had received a median of 7 lines of previous treatment, and the majority, or 84%, received more than 4 lines of therapy.
Prior treatments received included bortezomib (Velcade; 98%), carfilzomib (Kyprolis; 76%), lenalidomide (Revlimid; 100%), pomalidomide (Pomalyst; 92%), daratumumab (Darzalex; 100%), and isatuximab (3%). Notably, 76% of participants were refractory to bortezomib, 65% to carfilzomib, 90% to lenalidomide, 87% to pomalidomide, 100% to daratumumab, and 3% to isatuximab.
The median age of participants in the 3.4-mg/kg arm was 67 years, 57% were male, and 47% had high-risk cytogenetics. In this cohort, patients received a median of 6 previous lines of treatment, with 83% having received more than 4 lines of therapy.
Previous therapies received included bortezomib (98%), carfilzomib (65%), lenalidomide (100%), pomalidomide (85%), daratumumab (97%), and isatuximab (2%). Notably, 75% of participants were refractory to bortezomib, 58% to carfilzomib, 89% to lenalidomide, 78% to pomalidomide, 92% to daratumumab, and 1% to isatuximab.
Additional data indicated that the ORR in the 2.5-mg/kg cohort included a very good partial response (VGPR) or better in 19% (n = 18) of patients. An ORR of 34% was reported in the 3.4 mg/kg arm, which included a VGPR or better in 20% (n = 20) of patients. Additionally, 3 stringent complete responses or complete responses were reported in each cohort.
The median follow-up was 6.3 months in the 2.5-mg/kg cohort and 6.9 months in the 3.4-mg/kg cohort. Overall, the median duration of response (DOR) was not reached. At the data cutoff date, 18 patients who received the ADC at 2.5 mg/kg and 25 who received it at the 3.4-mg/kg dose experienced a DOR of 4 months or longer.
The authors noted that progression-free survival (PFS) follow-up was ongoing and participants were continuing on treatment. The median PFS reported was 2.9 months (95% CI, 2.1-3.7) in the 2.5-mg/kg cohort and 4.9 months (95% CI, 2.3-6.2) in the 3.4-mg/kg cohort.
With regard to safety, the toxicity profile of the ADC was found to be consistent with data that have previously been reported. The most commonly observed toxicities in the 2.5-mg/kg cohort included keratopathy/microcyst-like epithelial changes or MECs (71%), thrombocytopenia (38%), anemia (27%), blurred vision events (25%), nausea (25%), pyrexia (23%), increased aspartate aminotransferase (21%), infusion-related reactions (21%), and lymphopenia (20%).
“Despite advances in treatment, multiple myeloma remains incurable and patients continue to cycle through therapies, with their prognosis worsening with each relapse,” Katja Weisel, MD, deputy director and associate professor of Hematology/Oncology in the Department of Oncology, Hematology, and Bone Marrow Transplantation at the University Medical Centre Hamburg-Eppendorf, stated in the release. “The approval of [belantamab mafodotin], with its novel mechanism of action, represents a new class of treatment that patients can turn to when their cancer stops responding to other standard-of-care options.”
Belantamab mafodotin is the first anti-BCMA agent to receive approval in the European Union, according to GSK, the drug developer. In 2017, the agent was granted a PRIME designation and the Conditional Marketing Authorisation Application was reviewed under the European Medicines Agency’s accelerated assessment procedure.
In August 2020, the ADC received regulatory approval by the FDA for single-agent use in adult patients with relapsed/refractory multiple myeloma who received at least 4 previous therapies, including an anti-CD38 monoclonal antibody, a PI, and an IMiD.