The US Food and Drug Administration (FDA) has approved belantamab mafodotin (Blenrep®’ GSK; see ADC Drugmap), an antibody-drug conjugate (ADC) comprising a humanized BCMA (B-cell maturation antigen) conjugated to the cytotoxic agent monomethyl auristatin F (MMAF) via a non-cleavable linker, in combination with bortezomib (Velcade®; Takeda) and dexamethasone (BVd) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory (IMID) agent.
Granted initially accelerated approval in August 2020, based on the outcome of the DREAMM-2 clinical trial ( NCT03525678), GSK voluntarily withdrew belantamab mafodotin from the US market in 2023 after failing to demonstrate improved progression-free survival (PFS) in the DREAMM-3 confirmatory trial (NCT04162210).
This, however, was not the end of the road for belantamab mafodotin and GSK. Despite a serious setback in the United States, GSK continued exploring new Biologics License Applications based on updated results from the DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) Phase 3 trials.
Data from a post hoc subgroup analysis of the DREAMM-7 and DREAMM-8 clinical trials, presented at the the annual meeting of the American Society of Clinical Oncology (ASCO), held from May 30 – June 3, 2025 in Chicago, Illinois, demonstrated that patients with high-risk cytogenetic abnormalities (HRCAs), a patient subgroup that has a poor prognosis and required more efficacious treatments, benefited from treatment that included belantamab mafodotin.
The outcomes of this analysis demonstrated clinically meaningful PFS benefit, higher ORR, and a higher rate of deep responses, supporting the potential use of belantamab mafodotin as a standard-of-care regimen in this key patient population with a high unmet need. [1]
Based on this data, GSK submitted a new Biologics License Application (BLA) for belantamab mafodotin, which was accepted for review by the FDA in November 2024.
“The evidence from DREAMM-7 and DREAMM-8 supports our belantamab mafodotin 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,” explained Hesham Abdullah, MD, head of oncology research and development at GSK.
Following the publication of the FDA’s briefing document on belantamab mafodotin, GSK confirmed that the company remains confident in the benefit/risk profile of belantamab mafodotin in patients with relapsed or refractory multiple myeloma where there is high unmet need for novel treatment options that extend survival.
Concern over Ocular Events
However, in July 2025, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted against approving belantamab mafodotin for use in combination regimens for relapsed or refractory multiple myeloma due to concerns about ocular toxicity. But the ODAC’s vote is nonbinding and is generally considered a recommendation that helps the FDA reach a final regulatory decision.
Although nearly all patients participating in the clinical studies receiving belantamab mafodotin experienced at least 1 adverse event, the Oncologic Drugs Advisory Committee based their recommendation not to support approval of the drug on one key safety issue involving ocular events, a known adverse effect of belantamab mafodotin (in the in DREAMM-7 and DREAMM-8 studies ocular events were the most commonly reported adverse events in the belantamab mafodotin arms).*
These ocular events are primarily related to the small molecule payload of belantamab mafodotin, cys-mcMMAF, a microtubule inhibitor. Monomethyl auristatin F (MMAF) is known to be associated with ocular toxicities, including corneal events. However, these events are manageable and reversible using the prescribed dose reductions and/or dose delays utilized in the DREAMM-7 and DREAMM-8 studies. Furthermore, severe ocular events as a result of treatment with belantamab mafodotin, were infrequent, and the overall impact on reading,
driving, and health related Quality of Life (hrQoL) was limited.
In the DREAMM-7 and DREAMM-8 clinical studies, ocular events are ‘not absent’ in the comparator arms of these studies and, according to GSK, should therefor be considered when evaluating the ocular events in the belantamab mafodotin-containing arms of the study. The study results also demonstrated that the incidence of ocular events between the two arms was very similar Furthermore, there are, to-date, no confirmed reports suggesting permanent vision loss among the more that 7,500 patients who participated in GSK’s clinical trial program or in the clinic.
The FDA’s decision to grant full approval overrules the ODAC’s advice. While the FDA generally follows such a recommendation, they are bound to do so. Hence today’s decision allows GSK to relaunch belantamab mafodotin and return to the US market.
A different market
With the return of belantamab mafodotin, GSK is competing with other therapies, including Johnson & Johnson’s and Legend Biotech’s ciltacabtagene autoleucel (Carvykti®) in second-line treatment, Bristol Myers Squibb’s idecabtagene vicleucel (Abecma®), Pfizer’s elranatamab (Elrexfio®), and Johnson & Johnson’s teclistamab (Tecvayli®), all trying to secure a share of the market in later-line settings.
Despite growing competition, most approved therapies require a hospital setting. As a result, not all currently approved and available agent are available to all patients, In contrast, belantamab mafodotin, is, according to Tony Wood, Chief Scientific Officer, GSK., for the majority of patients available on an outpatient basis.
“There is an urgent need for new and novel therapies, as nearly all patients with multiple myeloma experience relapse and re-treating with the same mechanism of action often leads to suboptimal outcomes,” Wood said.
“As the only anti-BCMA agent that can be administered across healthcare settings, including in community centers where 70% of patients receive care, belantamab mafodotin fulfils a major patient need. We believe belantamab mafodotin can redefine treatment for patients with multiple myeloma in all parts of the world, and we are accelerating its development in earlier lines of therapy to support its use across all stages of this difficult-to-treat cancer,” Wood added.
Wood also points to the fact that while the FDA’s ODAC voted against the approval of belantamab mafodotin because of ocular toxicity concerns, each of the competing agents has its unique ‘adverse events’ profile.
Significant Milestone
“Today’s FDA approval of belantamab mafodotin is another significant milestone, providing potential for superior efficacy, including overall survival, to US patients,” Wood concluded.
“With the approval of belantamab mafodotin, we now have a community-accessible BCMA-targeting agent with the potential to improve outcomes for patients following two or more prior lines of treatment, where options are limited. This approval marks an important advance in the US relapsed/refractory treatment landscape,” noted Sagar Lonial, MD, Chief Medical Officer, Winship Cancer Institute of Emory University in Atlanta, Georgia, Chair of Emory Department of Hematology and Medical Oncology.
“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 belantamab mafodotin in combination to help patients achieve this,” explained Michael Andreini, President and Chief Executive Officer of the Multiple Myeloma Research Foundation and the Multiple Myeloma Research Consortium.
A common blood cancer
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable. This results in a significant unmet medical need for patients.[6][7] There are approximately 180,000 new cases of multiple myeloma diagnosed globally each year.
Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.[8] Many patients with multiple myeloma, including approximately 70% in the US, are treated in a community cancer setting, leaving an urgent need for new, effective therapies with manageable side effects that can be administered outside of an academic centre.[1][2][10][11]
With belantamab mafodotin approved, supported by data from the pivotal DREAMM-7 phase 3 trial (NCT04246047), a new treatment option is now available.
The DREAMM-7 trial, a part of the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical trial program, enrolled 494 participants who were randomized 1:1 to receive either BVd or DVd. Belantamab mafodotin was administered at a dose of 2.5mg/kg intravenously every 3 weeks in combination for the first 8 cycles, and then continued as a single agent.
The primary endpoint was PFS as per an independent review committee, with secondary endpoints including OS, duration of response (DOR), and minimal residual disease (MRD) negativity rate as assessed by next-generation sequencing. Other secondary endpoints include overall response rate (ORR), safety, and patient-reported and quality of life outcomes.
Study results
In patients who had two or more prior lines of therapy (3L+), including a proteasome inhibitor and an immunomodulatory agent, belantamab mafodotin in combination demonstrated a clinically meaningful 51% reduction in the risk of death [HR 0.49, 95% confidence interval (CI): 0.32-0.76] and a tripled median progression-free survival (PFS) of 31.3 months [95% CI: 23.5-NR)] versus 10.4 months [95% CI: 7.0-13.4] for a daratumumab-based triplet (DVd) [HR 0.31, 95% CI: 0.21-0.47]. The safety and tolerability profiles of the belantamab mafodotin combination were broadly consistent with the known profiles of the individual agents.
REMS supports
Working closely with the FDA, belantamab mafodotin is available through a new, streamlined Risk Evaluation and Mitigation Strategy (REMS). The new REMS supports appropriate use and patient safety while reducing administrative burden through simplified patient forms, removal of duplicative checklists, and efficient communication between healthcare professionals (HCPs) and either optometrists or ophthalmologists monitoring eye care. GSK will also offer Together with GSK, an optional patient support program available to all US patients prescribed belantamab mafodotin.
Data from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical trial programme will be submitted to the National Comprehensive Cancer Network (NCCN) guidelines this year. Recent results from the DREAMM studies, alongside emerging real-world evidence, provide a growing body of data for Blenrep.[4][5]
Ongoing development
GSK is advancing the DREAMM clinical program to demonstrate the potential benefit of belantamab mafodotin in earlier lines of treatment. Follow-up continues for overall survival (OS) in both DREAMM-7 and DREAMM-8 ,with data expected in early 2028, including in patients who have received only one prior line of therapy. DREAMM-10, a phase 3 trial in newly diagnosed transplant-ineligible patients, which represent over 70% of patients starting therapy, was initiated in Q4-2024.[3] This trial is designed to evaluate belantamab mafodotin plus lenalidomide and dexamethasone (BRd) versus daratumumab plus lenalidomide and dexamethasone (DRd).[3]
Interim efficacy and safety data for belantamab mafodotin as a first-line treatment are expected in early 2028, with enrollment expanded to US sites to increase US patient representation in the study population. GSK continues to work with the FDA for US patients.
Progression Free Survival
Progression Free Survival Data was presented at the American Society of Clinical Oncology (ASCO) Plenary Series in February 2024 and published in the New England Journal of Medicine.
In the primary endpoint of progression-free survival (PFS), a statistically significant and clinically meaningful improvement was observed with the belantamab mafodotin combination (n=243), showing a 59% reduction in the risk of disease progression or death (hazard ratio [HR]: 0.41 [95% confidence interval (CI): 0.31-0.53], p-value<0.00001) compared to the daratumumab combination (n=251). With a median follow-up of 28.2 months, the median PFS was 36.6 months (95% CI: 28.4-not reached [NR]) with the belantamab mafodotin combination compared to 13.4 months (11.1-17.5) in the daratumumab combination.
The PFS effect was observed across all prespecified subgroups, including those who were refractory to lenalidomide and those with high-risk cytogenetics. The safety and tolerability profile of the belantamab mafodotin combination was consistent with the known profile of the individual agents.
“The substantial progression-free survival benefit and strong overall survival trend compared to a daratumumab standard of care combination reinforce our belief in the potential for belantamab mafodotin used in combination to redefine the treatment of multiple myeloma at or after first relapse. We plan on sharing these results with health authorities worldwide.” GSK’s Abdullah observed.
The belantamab mafodotin combination also resulted in clinically meaningful improvements in all secondary efficacy endpoints, including a doubling of the complete response rate (stringent complete response plus complete response), minimal residual disease (MRD) negativity rate, and median duration of response (DOR). A strong and clinically meaningful overall survival (OS) trend was observed at the interim analysis, with a 43% reduction in the risk of death (HR: 0.57 [95% CI: 0.40-0.80], p-value=0.00049), but the OS difference has not yet met the interim criteria for statistical significance. OS follow-up continues, and further analyses are planned.
Overall Survival
The OS findings from DREAMM-7 build on previous data from the DREAMM-7 and DREAMM-8 trials, which showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for both belantamab mafodotin-based combinations compared with standard-of-care comparators.
“The compelling overall survival data from the DREAMM-7 trial establish the potential of Blenrep in combination to significantly extend the lives of patients with multiple myeloma at or after first relapse. This represents an important advancement that could redefine the treatment of relapsed or refractory multiple myeloma,” Abdullah said at the time of the release of the data.
With a median follow-up of 39.4 months, the analysis presented today shows a statistically significant 42% reduction in the risk of death among patients receiving the belantamab mafodotin combination (n=243) versus the daratumumab-based comparator (n=251) (HR 0.58; 95% CI: 0.43-0.79; p=0.00023). Although the median overall survival (mOS) was not reached in either arm of the study, the projected mOS for BVd is 84 months compared to 51 months for DVd
The three-year OS rate was 74% in the belantamab mafodotin combination arm and 60% in the daratumumab combination arm. The survival benefit favoring BVd was seen as early as four months and was sustained over time as illustrated by the separation of the lines in the Kaplan-Meier curve shown here.
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Note: * The most common reported adverse events included blurred vision and dry eye. Other reported adverse events included foreign body sensation in the eyes, photophobia, and eye irritation. The majority of these adverse events were of Grade 2 or 3.
Clinical trials
Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib, and Dexamethasone Versus Daratumumab, Bortezomib, and Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma (DREAMM 7) – ClinicalTrials.gov ID NCT04246047
Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma (DREAMM 8) – ClinicalTrials.gov ID NCT04484623
Highlights of Prescribing Information
Belantamab mafodotin (Blenrep®’ GSK) [Prescribing Information]
Bortezomib (Velcade®; Takeda)[Prescribing Information]
Ciltacabtagene autoleucel (Carvykti®; Johnson & Johnson’s and Legend Biotech)[Prescribing Information]
Idecabtagene vicleucel (Abecma®; Bristol Myers Squibb)[Prescribing Information]
Elranatamab (Elrexfio®; Pfizer)[Prescribing Information]
Teclistamab (Tecvayli®; Johnson & Johnson)[Prescribing Information]
References
[1] Beksac M, Pour L, Delimpasi S, Quach H, Vorobyev VI, Cavo M, Suzuki K, Robak P, Morris K, Lin CP, Garrobo-Calleja I, Fulci G, Manasanch E, Kremer B, Mateos MV, Athanasios Dimopoulos M.DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM): A subgroup analysis in patients with high-risk cytogenetic features. Journal of Clinical Oncology 2025 43:16_suppl, 7533-7533
[2] Bruno A, et al. Recent real-world treatment patterns and outcomes in US patients with relapsed/refractory multiple myeloma. Expert Review of Hematology. 2020; Volume 13, Issue 9:1017–1025 https://www.tandfonline.com/doi/full/10.1080/17474086.2020.1800451.
[3] Komodo claims data. Last accessed October 20, 2025.
[4] Hungria V, Robak P, Hus M, et al. Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024 Aug 1;391(5):393-407. doi: 10.1056/NEJMoa2405090. Epub 2024 Jun 1. PMID: 38828933.
[5] Hungria V, Robak P, H Marek, et al. Belantamab Mafodotin, Bortezomib, and Dexamethasone Vs Daratumumab, Bortezomib, and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Overall Survival Analysis and Updated Efficacy Outcomes of the Phase 3 Dreamm-7 Trial. Presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition. December 2024.
[6] Sung H, Ferlay J, Siegel R, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660.
[7] Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016;43(6):676–681.doi: 10.1053/j.seminoncol.2016.11.004.
[8] Global Cancer Observatory. International Agency for Research on Cancer. World Health Organization. Multiple Myeloma fact sheet. Online. Last accessed on October 20, 2025.
[9] Nooka AK, Kastritis E, Dimopoulos MA. Treatment options for relapsed and refractory multiple myeloma. Blood. 2015;125(20). doi:10.1182/blood-2014-11-568923.
[10] Gajra A, Zalenski A, Sannareddy A, et al. Barriers to Chimeric Antigen Receptor T-Cell (CAR-T) Therapies in Clinical Practice. Pharmaceut Med. 2022 Jun;36(3):163-171
[11] Crombie J, Graff T, Falchi L, et al. Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy. Blood (2024) 143 (16): 1565–1575.
[12] Relapsed/refractory multiple myeloma / Blenrep (Belantamab Mafodotin) Sponsor Briefing Document (version 2.0) Oncologic Drug Advisory Committee Meeting: 17 July 2025.
Featured image: GSK scientists in discussion. © 2017 – 2025 GSk Used with permission.
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