Belamaf Is Back: What Pharmacists Must Know About the Reapproval of Belantamab Mafodotin

Multiple myeloma (MM), the second most common hematologic malignancy in the United States, is an incurable disease characterized by continuous periods of remission and relapse. Emerging therapies have led to significant improvements in patient outcomes, enabling better responses and extended survival. Agents such as antibody-drug conjugates (ADCs), bispecifics, and chimeric antigen receptor T-cell therapy have advanced the treatment landscape for MM.

One such agent is belantamab mafodotin (belamaf, Blenrep; GlaxoSmithKline LLC), which was originally approved in 2020 before being pulled from the market. Although the approval was revoked, belamaf remained available through an expanded access approval program. In October 2025, the FDA reapproved the agent following positive data from the phase 3 DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) trials, which showed significant improvements in median progression-free survival (mPFS) when compared with daratumumab (Darzalex; Janssen Biotech, Inc).

Currently, belamaf is indicated in combination with bortezomib (Velcade; Takeda Pharmaceuticals America, Inc) and dexamethasone for adults with relapsed or refractory MM (RRMM) who have received at least 2 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD).

Exploring Belamaf’s Mechanism of Action

Belamaf is an ADC that binds to BCMA, the most commonly overexpressed protein in patients with MM, and is internalized into the cell to release a cytotoxic payload: monomethyl auristatin F (MMAF). MMAF is a microtubule inhibitor that disrupts microtubule dynamics, leading to cell cycle arrest and apoptotic death of myeloma cells.

Belamaf also initiates immune-mediated cell killing by recruiting immune effector cells, such as natural killer cells and macrophages. This drives antibody‑dependent cellular cytotoxicity and antibody‑dependent cellular phagocytosis, further promoting killing of BCMA‑expressing myeloma cells. This immune‑effector recruitment aspect is why it is sometimes compared with drugs such as rituximab (Rituxan; Biogen/Genentech, Inc).

“And so, this dual binding and modality mechanism really is unique for this medication in terms of indications….” explained Matthew Chui, PharmD, BCOP, a clinical pharmacy manager at the University of Miami.

The Dreamm-7 Trial

The efficacy and safety of belamaf were evaluated in the randomized, open‑label phase 3 DREAMM-7 study, whose data supported the reapproval. The trial evaluated adults with RRMM who had undergone at least 1 prior line of therapy, none of which were BCMA directed. Patients were excluded if they had refractory disease or were intolerant to daratumumab or bortezomib.

Patients were randomly assigned to receive either belamaf plus bortezomib and dexamethasone (BVd) or daratumumab plus bortezomib and dexamethasone (DVd). Belamaf was administered intravenously once every 3 weeks at a dose of 2.5 mg/kg, alongside 1.3 mg/m² of bortezomib subcutaneously on days 1, 4, 8, and 11 of each 3‑week cycle (cycles 1-8), and 20 mg of dexamethasone on the day of and the day after bortezomib. Following 8 cycles, belamaf was administered as a monotherapy from cycle 9 onward.

Patients in the DVd arm received daratumumab intravenously weekly for cycles 1 to 3, then once every 3 weeks for cycles 4 to 8, then once every 4 weeks from cycle 9 onward. The bortezomib and dexamethasone backbone was the same as the BVd arm.

In a subgroup analysis of patients with a median of 3 prior lines of therapy, the population was mostly male and White, with a median age of approximately 65 years. Most patients were Revised International Staging System stage I to II, with approximately 30% presenting with high-risk cytogenetics. Regarding prior therapies, approximately 19% of patients had disease that was refractory to a PI, 60% to an IMiD, and 70% had prior autologous stem cell transplant.

PFS, the trial’s primary end point, favored BVd over DVd at 31.3 months and 10.4 months, respectively, representing a nearly 3-fold improvement. This benefit was observed across other prespecified subgroups, such as those with extramedullary disease or high-risk cytogenetics. Although the overall survival (OS) was not reached at the time of reporting in the BVd arm, models predict a final median OS of about 75.5 months.

Understanding Belantamab Mafodotin Safety

Belamaf is associated with various adverse effects (AEs), of which ocular toxicities represent a key safety issue.

“Belamaf can cause ocular toxicity, defined as changes in the corneal epithelium and changes in BCVA based on an ophthalmic exam—including a slit lamp exam—or other ocular adverse events as defined by CTCAE [Common Terminology Criteria for Adverse Events],” said Chui.

According to the DREAMM-7 trial data, approximately 89% of patients experienced a reduction in best-corrected visual acuity (BCVA), with 57% experiencing grade 3 to 4 severity. Corneal findings were reported in 86% of patients (grade 3-4 in 72%). Blurred vision affected approximately two-thirds of patients (grade 3-4 in approximately 22%), while dry eye occurred in approximately 50% (grade 3-4 in approximately 7%). Other ocular AEs included photophobia, foreign body sensation, irritation or pain, cataracts, and visual impairment, affecting approximately 11% of patients (grade 3-4 in approximately 5%).

These ocular toxicities led to various dose interventions, including delays or interruptions (78%), reductions (44%), or permanent discontinuation (9%). Most ocular events improved to grade 1 or baseline with holds and dose modifications.

Patients also experienced hematologic AEs, including thrombocytopenia, which was reported in almost all patients (approximately 75%, grade 3-4). Neutropenia (grade 3-4) was seen in about half the patient population. The data also showed increased levels of liver enzymes, with aspartate aminotransferase elevations in approximately 88% of patients and alanine aminotransferase elevations in approximately 71%, though severe (grade 3-4) elevations were uncommon, occurring in only about 5%. Creatinine elevations were observed in just over half of patients.

“There’s also a risk of embryo fetal toxicity. Again, this is a drug that is linked to MMAF payload, so women of childbearing potential should be on contraception while on [belamaf] and for 4 months after the last dose,” explained Chui. “And [men] should be on contraception while on [belamaf] and for 6 months after the last dose.”

Other AEs included diarrhea (grade 3-4, in approximately 4% of patients), nausea (approximately 16%, mostly low‑grade), upper respiratory tract infection, hepatotoxicity (any grade, approximately 33%; grade 3-4, approximately 14%).

Dosing and Response Durability

As patients remained on belamaf, dosing intervals were commonly extended. In the early treatment phase (3 doses or fewer), the median dosing interval was approximately 3 weeks, which gradually increased to approximately 8 weeks by the ninth to twelfth dose and reached approximately 12 weeks among those who received the most doses (27-30). Notably, despite these dose reductions and extended intervals, response was maintained in approximately 70% of patients, and deepened in approximately 20%, meaning that almost 90% of patients either maintained or improved their clinical response even with modified scheduling.

Managing Ocular Toxicities With REMS

The belamaf Risk Evaluation and Mitigation Strategy (REMS) program exists to mitigate the risk of ocular toxicity associated with the drug. It reinforces the prescribing information, particularly requirements around ophthalmic monitoring and dosing. A baseline eye exam is required within 4 weeks before the first dose. Before each subsequent dose, an exam must be performed within 10 days, or sooner if new or worsening symptoms develop. Each exam includes BCVA assessment and a slit-lamp exam. Results are communicated to the prescriber to inform dosing decisions and REMS documentation.

Four stakeholders are involved in the REMS program: prescribers, health care settings, patients, and specialty distributors. Key roles include the authorized representative (AR), who is responsible for REMS compliance at each site; the prescriber designee, who can initiate forms but cannot authorize treatment; and the prescriber delegate, a REMS-certified prescriber who can authorize patient status forms when the enrolling prescriber is unavailable.

Prescribers must fulfill 3 requirements: complete a one-time REMS certification, enroll each patient individually, and submit a patient status form before every dose, confirming ophthalmic exam date, ocular grade, and dosing history. A designee may complete most fields, but a certified prescriber or delegate must authorize it.

In health care settings, sites must complete a one-time REMS certification by registering at blenreprems.com, designating an AR, and submitting an enrollment form. Sites must also provide a matching site identifier (NPI, DEA, or HIN) with the correct shipping address. Mismatches can delay orders. Optionally, sites within a system can form a network to allow REMS tracking of vial movement across locations.

Notable updates from the prior REMS: Any REMS-certified prescriber (not just the enrolling prescriber) can now authorize a patient status form, and prescriber authorization is now mandatory where it previously was not.

Looking Ahead With Belamaf

As belamaf becomes more widely used in the treatment of RRMM, pharmacists are uniquely positioned to support its safe and effective integration into clinical practice. With ocular toxicity representing the most significant safety concern, pharmacists play a critical role in educating patients about what to expect, reinforcing the importance of routine ophthalmic monitoring, and ensuring adherence to REMS requirements.

Beyond safety monitoring, pharmacists can help optimize dosing decisions, counsel patients on the management of other AEs such as hematologic and hepatic changes, and coordinate with prescribers and eye care providers to minimize treatment interruptions. As the MM landscape continues to evolve, pharmacists who are well versed in belamaf's mechanism, efficacy data, and REMS obligations will be essential partners in delivering the best possible outcomes for patients with RRMM.

REFERENCE

Chui M, Allen E. Advancing myeloma care: the pharmacist’s role in safe and effective use of blenrep. Presented at: Hematology/Oncology Pharmacy Association Annual Conference 2026. March 25-27, 2026. New Orleans, LA.