The approval was supported by findings from the phase 3 DREAMM-7 trial (NCT04246047), where BVd (n = 108) yielded a 51% reduction in the risk of death compared with daratumumab (Darzalex) plus bortezomib and dexamethasone (DVd; n = 109; HR, 0.49; 95% CI, 0.32-0.76). The median overall survival (OS) was not reached (NR) with BVd (95% CI, NR-NR) vs 35.7 months (95% CI, 21.2-NR) with DVd, and the median progression-free survival (PFS) extended to 31.3 months (95% CI, 23.5-NR) with BVd vs 10.4 months (95% CI, 7.0-13.4) with DVd (HR, 0.31; 95% CI, 0.21-0.47).2 The safety profile of BVd remained consistent with the known toxicities of the individual agents, reinforcing the regimen’s feasibility for use in clinical practice.
In interviews with OncLive®, Surbhi Sidana, MD, and Joshua Richter, MD, discussed how this approval reshapes clinical conversations, prompting oncologists to reassess where belantamab mafodotin may fit alongside CAR T-cell therapies and bispecific antibodies, how associated ocular toxicities can be managed without compromising efficacy outcomes, and what this evolving BCMA-directed treatment paradigm may look like for patients in both academic and community care settings.
Sidana serves as a medical oncologist at Stanford Health care, an associate professor of medicine, leader of the Myeloma CAR-T/Immunotherapy Program, leader of the Myeloma Disease Focused Group, and associate director for Clinical Research in the BMT and Cell Therapy Division at Stanford University and Stanford Cancer Institute in California. Richter serves as an associate professor of medicine in the Division of Hematology and Medical Oncology at the Tisch Cancer Institute, director of Multiple Myeloma at the Blavatnik Family- Chelsea Medical Center at Mount Sinai, and an assistant professor of medicine (hematology and medical oncology) at the Icahn School of Medicine at Mount Sinai in New York, New York.
OncLive: What is the significance of the FDA approval of BVd for patients with relapsed/refractory multiple myeloma?
Sidana: In 2025, we can control myeloma for a long time for many patients. With the CAR T-cell therapy data, maybe we can even call [some of] these patients functionally cured, but most patients will relapse. Having more options that can be given in diverse settings is important for our patients.
With belantamab mafodotin, one advantage is that it can be given in the community. It’s a BCMA-targeted drug. The other BCMA-targeted drugs we have are CAR T-cell therapies, which are approved after 1 prior line, and then we have BCMA-directed bispecific antibodies that are currently approved in later lines. [Additionally, in October 2025], we saw a news release [showing that the phase 3] MajesTEC-3 trial [(NCT05083169) of teclistamab-cqyv (Tecvayli) plus daratumumab and hyaluronidase-fihj (Darzalex Faspro) in patients with relapsed/refractory multiple myeloma] is a positive study.
Hopefully in the future, teclistamab and other BCMA-directed bispecific antibodies might be available in earlier lines, too. This would position us [to potentially have] 3 BCMA-directed options in 2026 and beyond. [To receive] bispecific antibodies and CAR T-cell therapy, patients need to be at a specialized treatment center. The bispecific antibodies are moving into the community [setting], but they still require intense monitoring for cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome.
With belantamab mafodotin, the advantage is [that] it can be given with fewer resources. It’s an antibody-drug conjugate [ADC], so [it] can be given to patients who can’t otherwise access CAR T-cell therapy or bispecific antibodies. Perhaps it can even be used after [those treatments], since we are not curing most of our patients [with those earlier lines of therapy].
Richter: One of the clear benefits with [belantamab mafodotin] is that it is targeting BCMA without affecting the T cells or needing T cells to be part of that activity. If you have a patient who does not have a robust T-cell repertoire, or has had suppressed counts, you can still use belantamab mafodotin. The drug is also highly combinable and works great with IMiDs and PIs. With the new data coming out, we can extend dosing from the original [protocol of] every 3 weeks to every 4 to 6 and even 8 or possibly 12 weeks, which is great for patients.
What clinical research supported the FDA’s decision to move belantamab mafodotin into the myeloma treatment paradigm?
Sidana: Belantamab mafodotin was evaluated in 2 studies, DREAMM-7 and the phase 3 DREAMM-8 study [NCT04484623]. In [DREAMM-7], it was combined with bortezomib and dexamethasone as BVd and compared with DVd. In [DREAMM-8], it was combined with an IMiD—pomalidomide [Pomalyst]—and dexamethasone [BPd] and compared with pomalidomide, bortezomib, and dexamethasone [PVd].
Both these studies were positive, with PFS benefits seen [with the belantamab mafodotin–based regimens]. An OS benefit also seen in DREAMM-7, which I was pleasantly surprised by because it is hard to beat daratumumab-based combinations; that is one of our premier drugs that has changed the treatment paradigm in myeloma. Those data were encouraging. [In DREAMM-8], the OS data are immature.
How should hematologists approach dosing with belantamab mafodotin when integrating this agent into real-world practice?
Sidana: The main concern that the FDA brought up at the [July 2025] Oncologic Drugs Advisory Committee meeting was the dosing. The dosing, per the FDA, was not completely fleshed out in the [DREAMM-7 and DREAMM-8] protocols. We know the starting dose, but is that the optimal dose? Probably not, because [patients often] need a lot of dose reductions and dose delays. I’d watch out for [that in clinical practice].
[An additional consideration] to be worked out in the real-world setting, is [how] dosing [may affect] adverse effect [AE] management. A big aspect of belantamab mafodotin, which is given once every 3 weeks (and the dosing can be spaced out once patients respond), is that it is associated with ocular AEs. The ocular AEs occur because the drug deposits in the cornea, [leading to] visual problems. These were seen in 80% of patients receiving belantamab mafodotin [in DREAMM-7], with grade 3 or 4 [ocular] AEs seen in 30% of patients.
This is going to be a challenge [as this combination in used in practice]. The study required dose delays or reductions, but the study environment was monitored closely [and was different from] when you give a drug that is FDA approved [in the real-world setting], especially in the community. It will be interesting to see if the FDA puts a Risk Evaluation and Mitigation Strategy requirement for these patients to have ophthalmologist visits, and [we will need to determine] how we can manage dose reductions and delays.
Richter: [Ocular toxicities] are typically self-limited, but they affect patients. Additionally, we still don’t know the entire optimal sequence of BCMA-directed therapies. If you want to give a patient a CAR T-cell therapy or a bispecific antibody, and you give them a BCMA-targeting ADC [first], will that negatively affect therapies down the road? I don’t know if that is clear yet.
What guidance would you offer to hematologists regarding real-world management of dosing and ocular toxicity with belantamab mafodotin?
Sidana: My one message to any provider that is going to adopt this therapy is: Do not be scared of dose delays and reductions. [Hold the dose] first, and then dose reduce at the first sign of any blurred vision or dry eye, because those are major toxicities we need to be cognizant of. They can be managed but require a lot of hands-on work for dose reduction and delays.
Consider, for a patient who is not being treated in an academic or referral center: is CAR T-cell therapy in their cards? Are bispecific antibodies in their cards? If so, it may make sense to hold off on [giving belantamab mafodotin] right away and send them for a consult for CAR T-cell therapy or bispecific antibodies, because for both CAR T-cell therapy and bispecific antibodies, prior BCMA-directed therapy exposure decreases the efficacy of those drugs. Truly consider the whole treatment paradigm for each patient, and maybe they can receive CAR T-cell therapy first and belantamab mafodotin later. If a patient can travel [to receive CAR T-cell therapy, that may be an option]. If a patient cannot travel, or their life circumstance will never allow them to [receive CAR T-cell therapy], that’s different. [It is important] to consider the whole picture.
What are your key takeaways for hematologists regarding the use of BVd in practice?
Sidana:Belantamab mafodotin is a drug that can be easily given but is associated with significant ocular AEs that can affect a patient’s quality of life. Dose holds, reductions, dose delays are the main methods of handling that. At any early sign of toxicity, hold the drug, delay the dose, and start again with a much lower dose. Sometimes, once [patients are] in response, we can even give [BVd with] quarterly dosing, so they don’t have to be on every-3-week dosing forever after the initial [cycles]. Especially if they’re having toxicity, [you can] space out [the doses].
The second important takeaway is that we will eventually have 3 players in the BCMA-targeted arena. Right now, we have CAR T-cell therapy and belantamab mafodotin, and in the future, we may also have bispecific antibodies, so treatment sequencing will become an issue. If a patient is eligible for CAR T-cell therapy or bispecific antibodies, those should be considered. Then perhaps belantamab mafodotin can be sequenced later, [if their situation] allows. If it doesn’t allow, that’s something to be cognizant of. For instance, if that patient cannot travel, [CAR T-cell therapy or bispecific antibody treatment] may not be possible or [a delay] may decrease the efficacy. However, maybe a year later, [they can receive] CAR T-cell therapy or a bispecific antibody.
References
- Blenrep approved by US FDA for use in treatment of relapsed/refractory multiple myeloma. News release. GSK. October 23, 2025. Accessed November 6, 2025. https://www.gsk.com/en-gb/media/press-releases/blenrep-approved-by-us-fda-for-use-in-treatment-of-relapsedrefractory-multiple-myeloma/
- Blenrep. Prescribing information. GSK; revised October 2025. Accessed November 7, 2025. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Blenrep/pdf/BLENREP-PI-MG.PDF
