The FDA has approved belantamab mafodotin (Blenrep, GlaxoSmithKline) in combination with bortezomib and dexamethasone for relapsed or refractory multiple myeloma (R/R MM) in adults after at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

Belantamab mafodotin is an antibody-drug conjugate (ADC) that targets B-cell maturation antigen. 

The approval marks the ADC’s return to the US market. Belantamab mafodotin was initially approved at monotherapy in 2020 for R/R MM in the fifth line, but GlaxoSmithKline pulled it off the market after a confirmatory trial fell short. 

In July, FDA’s Oncologic Drugs Advisory Committee voted 5-3 against approving the belantamab combination in the second-line setting, citing ocular toxicity, questions about dose optimization, and limited US enrollment in the approval trial. 

The agency instead granted a third-line indication and required a Risk Evaluation and Mitigation Strategy to help prevent serious eye injuries.

The approval was based on 217 patients in the DREAMM-7 trial who were randomly assigned evenly to receive either belantamab mafodotin or daratumumab on a background of bortezomib and dexamethasone, after two or more lines of treatment. Daratumumab plus bortezomib and dexamethasone is a standard treatment option for R/R MM. 

Median progression-free survival was 31.3 months in the belantamab arm but only 10.4 months in the daratumumab group. While median overall survival was not reached with belantamab, it was 35.7 months with daratumumab.

Ninety-two percent of belantamab recipients developed ocular toxicity, which was grade 3 in 77% and grade 4 in 83%. Labeling carries a boxed warning. 

The recommended belantamab mafodotin dose is 2.5 mg/kg once every 3 weeks in combination with bortezomib and dexamethasone for eight cycles, followed by belantamab mafodotin monotherapy at 2.5 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. 

Maker GlaxoSmithKline is continuing to develop the ADC for earlier treatment lines, including newly diagnosed transplant-ineligible patients.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com