Written By: Sheetal Barbade BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has approved Blenrep (Belantamab Mafodotin-blmf), developed by GlaxoSmithKline plc in combination with bortezomib and dexamethasone (BVd) for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least two prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD).
This approval, granted on October 23, 2025, marks a landmark re-entry for Blenrep into the U.S. market after its voluntary withdrawal in 2023. The decision recognizes significant improvements in survival demonstrated in the pivotal DREAMM‑7 trial.
About the Blenrep
Blenrep (Belantamab mafodotin-blmf) is an innovative antibody-drug conjugates (ADC) comprising two essential components: Belantamab and Mafodotin. The Belantamab part is a fully humanized anti-BCMA (B-cell maturation antigen) IgG1 monoclonal antibody, designed to bind selectively to the BCMA protein expressed on malignant plasma cells in multiple myeloma. The Mafodotin element refers to monomethyl auristatin F (MMAF), a potent microtubule-disrupting cytotoxic agent linked to the antibody via a stable, non-cleavable maleimidocaproyl linker.
Upon administration, Belantamab recognizes and attaches to BCMA on the surface of myeloma cells. The resulting ADC is internalized through receptor-mediated endocytosis, where, in the lysosomal environment, the Mafodotin (MMAF) payload is released. MMAF binds to tubulin, disrupting microtubule formation and causing cell cycle arrest at the G2–M phase, ultimately triggering apoptosis of myeloma cells. In parallel, the Belantamab antibody, afucosylated to enhance FcγRIIIa binding, stimulates antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), recruiting immune cells to further eliminate BCMA-positive tumor cells.
This targeted multi-modal mechanism delivered specifically by the dual components Belantamab and Mafodotin drives the antitumor efficacy of Blenrep, offering improved precision and reduced systemic toxicity compared to traditional chemotherapeutic approaches.
About Multiple Myeloma
Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells within the bone marrow, leading to bone lesions, anemia, renal dysfunction, and immunosuppression. It remains an incurable but treatable disease with a median survival of 5–10 years. Despite major advances using proteasome inhibitors, immunomodulatory drugs, and CAR‑T cell therapies, most patients relapse. Among relapsed or refractory populations, particularly those with prior exposure to PI and IMiD, outcomes remain poor and therapeutic options are limited.
Blenrep provides a community-accessible, off-the-shelf BCMA-targeted option that helps expand treatment beyond specialized centers.
Clinical Evidence: DREAMM-7 Trial
Study Design
The DREAMM-7 Phase 3 trial (NCT04246047) was a robust multicentre, open-label, randomized investigation assessing the efficacy and safety of Blenrep (belantamab mafodotin-blmf) in combination with bortezomib and dexamethasone (BVd) compared to a standard-of-care regimen of daratumumab plus bortezomib and dexamethasone (DVd). The study enrolled 494 adult patients with relapsed or refractory multiple myeloma who had progressed after at least one prior line of therapy. Participants were randomized in a 1:1 ratio to receive either the BVd or DVd regimen. Blenrep was administered at a dose of 2.5 mg/kg intravenously every three weeks with concurrent bortezomib and dexamethasone for the initial eight cycles, followed by maintenance Blenrep monotherapy. The primary endpoint was progression-free survival (PFS), with key secondary endpoints including overall survival (OS), duration of response (DOR), minimal residual disease (MRD) negativity, overall response rate (ORR), and patient-reported outcomes.
Results
Results from DREAMM-7 showed the BVd combination provided a clinically meaningful advantage over the DVd regimen. Median PFS in the BVd arm was 31.3 months versus 10.4 months with DVd, representing a 51% reduction in the risk of progression or death (HR ≈ 0.49). The overall survival was also significantly prolonged for patients receiving BVd, with a hazard ratio of 0.48 and interim data suggesting durable survival improvement at 30 months. The overall response rate (ORR) was 81% for BVd compared to 69% for DVd, with earlier and deeper responses observed in the Blenrep combination group. MRD negativity was achieved in a greater proportion of BVd-treated patients, indicating deeper molecular remission. These data, first presented at the ASCO Plenary Series and subsequently reported in NEJM and Lancet journals, establish Blenrep-based therapy as a promising new standard for relapsed or refractory multiple myeloma
Safety and Tolerability Profile
The BVd combination exhibited a manageable safety profile consistent with previous Belantamab experiences. Most common adverse events (≥10%) included keratopathy, thrombocytopenia, fatigue, nausea, and infusion-related reactions. Ocular adverse events were predominantly reversible and managed through dose modification and monitoring. To ensure safe use, the FDA approved streamlined REMS (Risk Evaluation and Mitigation Strategy) to facilitate access while continuing ophthalmologic precautions. No new safety signals were detected, and the combination safety was consistent with standard care regimens.
Key Opinions
Dr. Sagar Lonial, MD, Chief Medical Officer at Winship Cancer Institute remarked: “With the approval of Blenrep, we now have a community-accessible BCMA-targeting agent with potential to improve survival outcomes for relapsed or refractory multiple myeloma patients, where treatment options remain limited.”
Tony Wood, GSK’s Chief Scientific Officer, said: “This FDA approval represents a significant milestone for patients with multiple myeloma. Nearly all patients will relapse, and accessible options like Blenrep BVd address an urgent need for effective BCMA-directed therapies.”
Michael Andreini, President and Chief Executive Officer of the Multiple Myeloma Research Foundation and the Multiple Myeloma Research Consortium, stated: “The reality for most patients with multiple myeloma is a relentless cycle of remission and relapse, as their disease becomes refractory to treatments. Patients urgently need more effective treatment options that can offer more quality time with their loved ones. We see the potential for Blenrep in combination to help patients achieve this.
Implications for Public Health
This approval re-establishes BCMA antibody-drug conjugates within the U.S. myeloma treatment landscape, offering a non–cell-based BCMA therapy with durable efficacy and manageable toxicity. The community-accessible profile of Blenrep BVd ensures broader reach beyond tertiary cancer centers, potentially reducing disparities in access to advanced myeloma care. As GSK’s ongoing DREAMM clinical program explores earlier-line deployment (DREAMM‑8/9), Blenrep may reshape multiple myeloma treatment sequencing globally.
Future Plan
GSK continues to advance Blenrep’s clinical development in multiple myeloma with pivotal trials such as DREAMM-8 and DREAMM-10. DREAMM-8 is evaluating Blenrep combined with pomalidomide and dexamethasone for patients who have received at least one prior line of therapy, while DREAMM-10 aims to assess combinations in earlier-line settings to establish broader utility for newly diagnosed or transplant-ineligible patients. Results from these studies will help define Blenrep’s role across more stages of multiple myeloma management.
Brief Background on 2023 Market Withdrawal
Blenrep was originally granted accelerated FDA approval in August 2020 for heavily pretreated relapsed or refractory multiple myeloma based on response rates from the DREAMM‑2 trial. However, as required under the accelerated approval pathway, the confirmatory DREAMM‑3 Phase 3 study comparing Blenrep monotherapy to pomalidomide plus dexamethasone did not meet its primary endpoint of progression‑free survival superiority.
Following the negative outcome and an FDA Oncologic Drugs Advisory Committee (ODAC) recommendation against continued approval, GSK voluntarily withdrew Blenrep from the U.S. market in late 2022, finalizing the withdrawal process in early 2023. The decision was not safety‑related, but a consequence of failing to meet confirmatory efficacy criteria required under the accelerated approval framework.
During the transition, patients who were benefitting from Blenrep were offered continued access under a compassionate use program, while GSK advanced ongoing confirmatory combination trials including DREAMM‑7 and DREAMM‑8 that later demonstrated substantial efficacy and supported the drug’s re‑approval in 2025.
References
Blenrep approved by US FDA for use in treatment of relapsed/refractory multiple myeloma, 23 October 2025, GSK, https://www.gsk.com/en-gb/media/press-releases/blenrep-approved-by-us-fda-for-use-in-treatment-of-relapsedrefractory-multiple-myeloma/
Hungria, Vania et al, Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial, The Lancet Oncology, Volume 26, Issue 8, 1067 – 1080
DREAMM 7 Trial, https://dreammtrials.com/dreamm7.html
DREAMM 8 Trial, https://dreammtrials.com/dreamm8.html
DREAMM-10 Trial, https://dreammtrials.com/dreamm10.html
Vania Hungria et al, Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma, N Engl J Med 2024;391:393-407, VOL. 391 NO. 5, DOI: 10.1056/NEJMoa2405090
GSK provides an update on Blenrep (belantamab mafodotin-blmf) US marketing authorisation, 22 November 2022, GSK, https://www.gsk.com/en-gb/media/press-releases/gsk-provides-update-on-blenrep-us-marketing-authorisation/
Highlights of prescribing information, BLENREP (belantamab mafodotin-blmf) for injection, for intravenous use, https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Blenrep/pdf/BLENREP-PI-MG.PDF
Summary Box
Attribute | Detail |
Drug Name | Blenrep (belantamab mafodotin-blmf) |
Developer / MAH | GlaxoSmithKline plc (GSK) |
Drug Class | Anti-BCMA antibody–drug conjugate (ADC) |
Indication | Relapsed/refractory multiple myeloma (≥2 prior lines including PI & IMiD) |
Combination | Bortezomib + Dexamethasone (BVd) |
Clinical Trial | DREAMM‑7 (Phase 3, n=494) |
Efficacy Outcome | 51% reduction in death risk; median PFS 31.3 vs 10.4 months |
Approval Date | October 23, 2025 |
REMS Program | Streamlined for corneal monitoring |