The FDA has approved GlaxoSmithKline’s (GSK’s) Blenrep (belantamab mafodotin-blmf) in combination with bortezomib and dexamethasone (BVd) for adults with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
The decision, announced October 23, 2025, followed an extended review period set earlier this year and marks Blenrep’s return to the US market after its 2022 withdrawal.
Multiple myeloma is a cancer of antibody-producing plasma cells. It is generally treatable but not curable, and most patients eventually relapse despite multiple lines of therapy.
How Blenrep Works
Blenrep is an antibody-drug conjugate targeting BCMA. It links a humanized antibody to auristatin F via a non-cleavable connector, delivering the chemotherapy payload into malignant plasma cells.
The product was previously available in the US as monotherapy for heavily pretreated disease and was voluntarily withdrawn to complete additional confirmatory studies.
Results from DREAMM-7
Efficacy for this approval was established in DREAMM-7, a randomized, open-label, multicenter Phase III trial that enrolled 494 participants with at least one prior line of therapy. The FDA based its decision on outcomes in the subgroup with two or more prior lines.
Patients received either BVd or a comparator regimen of daratumumab, bortezomib and dexamethasone (DVd). The primary endpoint was progression-free survival (PFS, time to progression or death); secondary endpoints included overall survival (OS), duration of response and minimal residual disease negativity.
In the ≥2 prior-lines subgroup, belantamab mafodotin-blmf plus bortezomib and dexamethasone achieved a median PFS of 31.3 months versus 10.4 months with DVd (HR 0.31). Median OS had not yet been reached in the BVd arm, compared with 35.7 months in the DVd group.
Treatment was given intravenously (IV) every three weeks with the combination for the first eight cycles, followed by belantamab mafodotin-blmf alone until progression or unacceptable toxicity.
Safety and Risk Management
The prescribing information includes a boxed warning for ocular toxicity.
The Blenrep label recommends baseline and regular ophthalmic exams, preservative-free artificial tears from the first infusion through end of therapy and avoiding contact lenses.
In DREAMM-7, eye-related adverse events occurred in 92% of patients receiving belantamab mafodotin-blmf, with Grade 3 to 4 (severe) events in 77%. Most patients required dose modifications.
Because of this risk, Blenrep is available only through an FDA-required Risk Evaluation and Mitigation Strategy (REMS) program intended to support appropriate use and streamline coordination with eye-care specialists.
Other warnings and precautions include thrombocytopenia and embryo-fetal toxicity.
Next Steps for GSK
GSK stated that Blenrep is currently the only anti-BCMA therapy accessible in community oncology settings, which are outpatient cancer clinics outside major academic centers where most US patients receive care.
The company is advancing the DREAMM program to evaluate earlier-line use, including DREAMM-8 (with pomalidomide and dexamethasone) and DREAMM-10 (in newly diagnosed, transplant-ineligible patients).
GSK also plans to submit DREAMM data to the NCCN guidelines and anticipates follow-up survival readouts in 2028
Outside the US, Blenrep combinations are already authorized for relapsed or refractory multiple myeloma in several regions, including the EU, UK, Japan, Canada, Switzerland and Brazil, with reviews ongoing in additional markets such as China.
Beyond BVd, BCMA-directed options in later lines include bispecific antibodies like Tecvayli (teclistamab) and Elrexfio (elranatamab) (both under accelerated approval after ≥4 prior lines), and CAR-T therapies Abecma (ide-cabtagene vicleucel) and Carvykti (ciltacabtagene autoleucel). These modalities differ in logistics, monitoring needs and where they are used in the treatment sequence.
In parallel, later-line research is also moving beyond BCMA to other targets such as GPRC5D, a myeloma-associated surface protein distinct from BCMA. An early-phase study of IASO Biotherapeutics’ RD118 (a GPRC5D-directed CAR-T) in heavily pretreated patients reported a 94% response rate and 18.2-month median PFS, with mostly low-grade cytokine release syndrome (CRS).
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