The European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion for belantamab mafodotin as a monotherapy in the treatment of adult patients with multiple myeloma who have received at least 4 prior therapies and whose disease is refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and aCD38-directed monoclonal antibody.
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for belantamab mafodotin as a monotherapy in the treatment of adult patients with multiple myeloma who have received at least 4 prior therapies and whose disease is refractory to at least 1 proteasome inhibitor (PI), 1 immunomodulatory agent (IMiD), and aCD38-directed monoclonal antibody, according to an announcement from GlaxoSmithKline (GSK), the developer of the antibody-drug conjugate (ADC).1
“Today’s positive opinion from the CHMP is an important step in helping patients suffering from relapsed/refractory multiple myeloma who currently have limited options and poor outcomes,” Axel Hoos, senior vice president and head of oncology R&D at GSK, stated in a press release. “If approved, belantamab mafodotin will provide patients and physicians across much of Europe with a first-in-class anti-BCMA treatment option that works differently from other available therapies for this incurable disease.”
In 2017, the novel agent was granted PRIME designation and the Conditional Marketing Authorization Application (CMAA) was reviewed per the EMA’s accelerated assessment protocol; this is given if CHMP decides that the therapy in question is of major interest regarding a public health perspective.
The CMAA was based on data from the pivotal phase 2 DREAMM-2 trial, which demonstrated that the ADC resulted in a 31% overall response rate (ORR; 97.5% CI, 20.8%-42.6%) in patients with relapsed/refractory multiple myeloma who had been given the recommended dose of 2.5 mg/kg.2 Patients who received the ADC at a dose of 3.4 mg/kg experienced an even higher ORR, at 34% (97.5% CI, 23.9%-46.0%). Of note, both ORRs were assessed via an independent review committee.
From June 18, 2018 through January 2, 2019, the open-label trial enrolled a total of 196 patients with relapsed/refractory disease to the intent-to-treat population. Participants were then randomized 1:1 to receive either intravenous belantamab mafodotin at the 2.5-mg/kg dose (n = 97) or the 3.4-mg/kg dose (n = 99) every 3 weeks until disease progression or intolerable toxicity.
To be eligible for enrollment, patients had to have an ECOG performance status of 0 to 2, experienced progressive disease on 3 or more lines of treatment, been refractory to a PI and an IMiD, and were either refractory or intolerant to a CD38-directed monoclonal antibody.
Patient baseline characteristics were well balanced between the 2 treatment arms. The median age in the 2.5-mg/kg cohort was 65 years, almost half (53%) were male and 42% had high-risk cytogenetics. Notably, patients were heavily pretreated, with a median of 7 prior lines of treatment received (range, 3-21). Eighty-four percent of participants had received more than 4 lines of previous treatment, which included bortezomib (Velcade; 98%), carfilzomib (Kyprolis; 76%), and isatuximab-irfc (Sarclisa; 3%). All participants had previously received lenalidomide (Revlimid). Seventy-six percent of patients were refractory to bortezomib, 65% to carfilzomib, 90% to lenalidomide, 87% to pomalidomide, 3% to isatuximab, and 100% to daratumumab.
Additional results from the trial indicated a 31% ORR with belantamab mafodotin in patients who received the agent at the 2.5 mg/kg dose; this included a very good partial response (VGPR) or better achieved in 19% of patients. In the 3.4-mg/kg cohort, patients experienced a 34% ORR with a VGPR or better reported in 20% of patients. In each cohort, 3 stringent complete responses (sCRs) or complete responses (CRs) were reported.
For the 2.5-mg/kg cohort, the median follow-up was 6.3 months compared with 6.9 months in the 3.4-mg/kg cohort. The median duration of response (DOR) had not yet been reached. The median progression-free survival (PFS) was 2.9 months and 4.9 months in the 2.5-mg/kg cohort and the 3.4-mg/kg cohort, respectively.
Updated data from the trial presented during the 2020 ASCO Virtual Scientific Program revealed an ORR of 32% (97.5% CI, 21.7%-43.6%) in the 2.5-mg/kg cohort and 35% (97.5% CI, 23.9%-46.0%) in the 3.4-mg/kg cohort at the 13-month follow-up.3
At this time, the DOR had still not been reached in either cohort; however, the median DOR was estimated to be 11.0 months (95% CI, 4.2–not reached [NR]) and 6.2 months (95% CI, 4.8-NR) in the 2.5-mg/kg and 3.4-mg/kg cohorts, respectively. Moreover, over half of the participants who experienced a response to the ADC in both cohorts achieved a VGPR or better (58% in the 2.5-mg/kg cohort vs 66% in the 3.4-mg/kg cohort. Eleven patients experienced a VGPR in the 2.5-mg/kg cohort with 5 having a CR and 2 having a sCR. Eighteen patients experienced a VGPR in the 3.4-mg/kg cohort, with 3 experiencing a CR and 2 having a sCR.
Regarding safety, all-grade adverse effects (AEs) were experienced by 98% in the lower-dose cohort and all patients in the higher-dose cohort; treatment-related AEs occurred in 88% versus 95% of patients, respectively. Grade 3 or higher toxicities occurred in 84% of those across cohorts; among the most common were keratopathy (46% vs 42% in the lower- and higher-dose cohorts, respectively), anemia (21% vs 27%), thrombocytopenia (22% vs 32%), decreased lymphocyte count (13% vs 7%), and neutropenia (11% vs 7%).
Data from another analysis of the DREAMM-2 trial, regarding outcomes of patients with high-risk cytogenetics, were also presented during the 2020 ASCO meeting. The ORRs were found to be comparable in both the high- and standard-risk patients. Although some numerical differences had been reported, they were not determined to be of statistical significance.4
In January 2020, the FDA granted priority review to a biologics license application for belantamab mafodotin for use in patients with relapsed/refractory multiple myeloma who received previous treatment with an IMiD, a PI, and an anti-CD38 monoclonal antibody. On July 14, 2020, the FDA’s Oncologic Drugs Advisory Committee voted 12 to 0 in favor of approving the ADC for select patients with relapsed/refractory disease who had previously received at least 4 prior therapies.