The FDA’s Oncologic Drugs Advisory Committee (ODAC) has voted against the overall benefit-risk profile of Blenrep (belantamab mafodotin-blmf) combinations at the proposed dosage for adults with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior line of therapy. The committee cited significant safety concerns, particularly persistent ocular adverse events (AEs), such as corneal ulcers and keratopathy, which were observed in the Phase III DREAMM-7 and DREAMM-8 trials, according to Reuters.

The panel voted 5-3 and 7-1, respectively, against the benefit-risk profiles of Blenrep when combined with bortezomib or pomalidomide—both approved cancer therapies—and dexamethasone, a commonly used steroid, citing concerns at the proposed dosages.^1,2

Can Blenrep Still Find a Path Forward Despite ODAC’s Negative Vote?

Despite the advisory committee’s vote, GSK emphasized the potential impact of Blenrep combinations and reiterated its commitment to advancing treatment options for RRMM patients.

“[RRMM] treatment could be transformed by additional, efficacious treatment options with manageable side effects and community-based administration,” said Hesham Abdullah, SVP, global head oncology, GSK, in a December 2024 press release. “The evidence from DREAMM-7 and DREAMM-8 supporting our Blenrep combinations submission has been further strengthened by the statistically significant overall survival results from the DREAMM-7 trial. We look forward to working with the FDA on this review.”³

Inside the DREAMM-7 and DREAMM-8 Trials

• The multicenter, open-label, randomized Phase III DREAMM-7 and DREAMM-8 trials evaluated the efficacy and safety of Blenrep. In DREAMM-7, 494 patients who had received at least one prior line of therapy and experienced disease progression were randomly assigned in a 1:1 ratio to receive Blenrep with bortezomib and dexamethasone or a comparator regimen of daratumumab, bortezomib, and dexamethasone.
• In DREAMM-8, 302 patients—who were more heavily pretreated and had all previously received lenalidomide—were randomly assigned in a 1:1 ratio to receive Blenrep with pomalidomide and dexamethasone or a combination of bortezomib, pomalidomide, and dexamethasone.
• The primary endpoint of both trials was progression-free survival (PFS) assessed by an independent review committee, with key secondary endpoints including overall survival, duration of response (DREAMM-7 only), and minimal residual disease negativity rates assessed by next-generation sequencing.

Key Efficacy and Safety Findings

• Results from both trials showed that Blenrep-based combinations delivered clinically meaningful improvements across all secondary efficacy endpoints, offering deeper and more durable responses than the respective standard-of-care regimens.
• In DREAMM-7 specifically, Blenrep reduced the risk of disease progression or death by 59% compared to the daratumumab combination, achieving a median PFS of 36.6 months with a median follow-up of 28.² months.
• Reported grade 3 or higher non-ocular AEs included thrombocytopenia, neutropenia, pneumonia, and anemia.³

Regulatory Background and Future Outlook

Blenrep was first granted accelerated approval by the FDA in August 2020 as a monotherapy treatment for adult patients with RRMM who had received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.4 However, the treatment was withdrawn from the market in November 2022 due to results from the Phase III DREAMM-3 confirmatory trial, which failed to meet accelerated approval requirements set by the FDA.⁵

Despite the outcome, the FDA is expected to make its final decision ahead of the Prescription Drug User Fee Act date on July 23, 2025. GSK stated that it remains confident in the potential of Blenrep to address unmet needs in patients with RRMM.¹

Following the 2022 market withdrawal, Sabine Luik, chief medical officer, GSK, stated: “We respect the Agency’s approach to the accelerated approval regulations and associated process. Multiple myeloma is a challenging disease, with poor outcomes for patients whose disease has become resistant to standard-of-care treatments. We will continue the DREAMM clinical trial program and work with the US FDA on a path forward for this important treatment option for patients with multiple myeloma.”⁵

References

1. GSK provides update on US FDA advisory committee review of Blenrep (belantamab mafodotin-blmf) combinations for patients with relapsed/refractory multiple myeloma. GSK. July 18, 2025. Accessed July 18, 2025. https://www.gsk.com/en-gb/media/press-releases/gsk-provides-update-on-us-fda-advisory-committee-review-of-blenrep-belantamab-mafodotin-blmf-combinations-for-patients-with-relapsedrefractory-multiple-myeloma/
2. FDA Accepts GSK’s Biologics License Application of Blenrep for Relapsed or Refractory Multiple Myeloma. PharmExec. December 2, 2024. Accessed July 18, 2025. https://www.pharmexec.com/view/fda-accepts-gsk-biologics-license-application-blenrep-relapsed-refractory-multiple-myeloma
3. GSK's blood cancer drug fails to secure US FDA advisers' support. Reuters. July 17, 2025. Accessed July 18, 2025. https://www.reuters.com/business/healthcare-pharmaceuticals/gsks-blood-cancer-drug-fails-secure-us-fda-advisers-support-2025-07-17/?utm_source=chatgpt.com
4. FDA Approves Blenrep. Drugs.com. August 5, 2020. Accessed July 18, 2025. https://www.drugs.com/newdrugs/fda-approves-blenrep-belantamab-mafodotin-blmf-patients-relapsed-refractory-multiple-myeloma-5316.html
5. GSK Provides an Update on Blenrep (belantamab mafodotin-blmf) US Marketing Authorization. Drugs.com. November 22, 2025. Accessed July 18, 2025. https://www.drugs.com/nda/blenrep_221122.html