FDA panel supports approval of belantamab mafodotin for relapsed/refractory myeloma
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An FDA advisory committee today voted unanimously to recommend approval of belantamab mafodotin for patients with relapsed or refractory multiple myeloma, concluding the clinical benefits outweigh potential risks that include keratopathy.
“It’s clear that this is an active agent and that the toxicity is not life-threatening,” Philip Hoffman, MD, professor of medicine at University of Chicago, said before the vote by the Oncologic Drugs Advisory Committee. “In many instances it is comfort-threatening, but I think patients are willing to take this risk. Mitigation plans laid out by the manufacturer, including exams before dosing and grading systems, are reasonable and address toxicity concerns.”
The FDA granted priority review to belantamab mafodotin (GSK2857916, GlaxoSmithKline) in January for the treatment of patients with relapsed or refractory multiple myeloma who previously received an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.
Belantamab mafodotin, an investigational anti-B-cell maturation antigen monoclonal antibody-drug conjugate, demonstrated clinically meaningful response rates among patients with heavily pretreated multiple myeloma, according to results of the randomized phase 2 DREAMM-2 trial published in The Lancet Oncology.
However, many patients experienced ocular toxicity in the form of keratopathy, which can lead to decreased visual acuity or severe vision loss.
Dose modifications may be needed to resolve toxicity issues, researchers noted.
“Oncologists are quick learners; we are used to unusual toxicities with some of the targeted agents,” Grzegorz S. Nowakowski, MD, consultant in the division of hematology of the department of internal medicine, as well as associate professor of medicine and oncology at Mayo Clinic, said during the meeting. “The programs put in place [by the manufacturer] are very reassuring that this drug is safe, and for these reasons, I support using this therapy.”
The randomized DREAMM-2 trial included 196 patients with relapsed or refractory multiple myeloma. Researchers randomly assigned 97 patients (median age, 65 years; interquartile range [IQR], 60-70) to 2.5 mg/kg belantamab mafodotin and 99 patients (median age, 67 years; IQR, 61-72) to a 3.4 mg/kg dose.
Patients received the regimens via IV infusion every 3 weeks on day 1 of each cycle until disease progression or unacceptable toxicity.
The trial participants had a median seven prior lines of treatment, were refractory to an immunomodulatory drug and a proteasome inhibitor, and were refractory to and/or intolerant of an anti-CD38 antibody.
The proportion of patients who achieved overall response per independent committee review served as the study’s primary endpoint. Researchers also evaluated safety among patients who received at least one dose of belantamab mafodotin.
Results showed an overall response rate of 31% (97.5% CI, 20.8-42.6) in the 2.5 mg/kg group compared with 34% (97.5% CI, 23.9-46) in the 3.4 mg/kg group. These included very good partial responses or better among 18% of patients in the lower-dose group and 20% of patients in the higher-dose group.
Clinical benefit, defined as minimal response or better as assessed by independent committee review, had been achieved by 34% (97.5% CI, 23.5-45.8) of patients in the 2.5 mg/kg group and 39% (97.5% CI, 28.5-51.1) of those in the 3.4 mg/kg group.
Median duration of response had not been reached at median follow-up of 6.3 months (IQR, 3.7-7.7) in the 2.5 mg/kg group and 6.9 months (IQR, 4.8-7.9) in the 3.4 mg/kg group. At data cutoff on June 21, 2019, researchers observed responses of 4 months or longer among 18 patients in the 2.5 mg/kg group and 25 patients in the 3.4 mg/kg group.
OS and PFS data remained immature. However, 32 deaths occurred in the 2.5 mg/kg group vs. 31 deaths in the 3.4 mg/kg group, with median PFS of 2.9 months (95% CI, 2.1-3.7) vs. 4.9 months (95% CI, 2.3-6.2).
Most patients in both cohorts experienced keratopathy, including 71% in the 2.5 mg/kg cohort and 75% in the 3.4 mg/kg cohort. Common grade 3 or grade 4 adverse events among safety-evaluable patients included keratopathy (27% vs. 21%), thrombocytopenia (20% vs. 34%) and anemia (20% vs. 25%).
“This has a very good response rate compared [with] other agents, and I really like the durability of response,” Thomas Uldrick, MD, MS, deputy head of global oncology and associate professor in the clinical research division at Fred Hutchinson Cancer Research Center, said during the meeting. “I think the toxicity, although unique to this agent, can be mitigated with patient education and partnerships between oncologists and ophthalmologists.”
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