Key Points :
GSK's Blenrep approved by European Commission as combination therapy for relapsed/refractory multiple myeloma.
Phase III trials reported significant enhancement of survival compared to regimens of standard-of-care.
Important Background :
Blenrep (belantamab mafodotin) is a novel antibody-drug conjugate that has been engineered to be selective against multiple myeloma via the B-cell maturation antigen (BCMA), which is highly highly expressed on tumor plasma cells. Its action is such that it gives targeted delivery of the drug to cancer cells with minimal harm to the healthy tissues. Approved in 2020 under priority programs, Blenrep was voluntarily withdrawn in 2022 from some markets following a non-met demonstration trial. However, GSK persisted with the attempts at creating value in combination regimens.
To further establish the therapeutic benefit of Blenrep, GSK started two big Phase III studies, DREAMM-7 and DREAMM-8. In the DREAMM-7 trial, Blenrep plus bortezomib and dexamethasone (BVd) regimen was compared head-to-head against control daratumumab regimen. The study demonstrated 42% risk reduction of death and statistically and clinically significant delay in progression-free survival among patients treated with the Blenrep-based regimen. This not only demonstrated statistical significance but also clinical significance benefit.
In the DREAMM-8 trial, Blenrep was given with pomalidomide and dexamethasone and compared with the triple standard treatment of bortezomib, pomalidomide, and dexamethasone. The outcome confirmed the efficacy of Blenrep with extensively longer progression-free survival and good safety profile as a second-line therapy in patients already treated with lenalidomide.
Of the most frequent adverse effects of Blenrep has been ocular toxicity, primarily keratopathy and changes in vision. Although severe side effects, in clinical trials they were controlled through dose reduction and active eye monitoring regimens. Good clinicians prefer to use it in spite of risk owing to the efficacy of the drug in patients who are already heavily pretreated.
Despite the European Union now having approved the treatment, the United States FDA is not yet convinced. An advisory panel recently turned down the approval due to safety concerns, and it has left the FDA again to delay its review timeline. GSK, however, remains in discussions with regulators worldwide in a bid to obtain wider access to the medication.
Worldwide, relapsed or refractory multiple myeloma is a very common blood cancer, and although life has been prolonged by new medicines, relapsed or refractory disease remains an enormous clinical challenge. Blenrep approval in combination regimens is the eagerly awaited addition to the armory and demonstrates GSK's ambition in oncology to innovate.