REMS: FDA approved a risk evaluation and mitigation strategy (REMS) for belantamab mafodotin-blmf to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of belantamab mafodotin-blmf and consists of the following: elements to assure safe use and an implementation system. See the FDA REMS page ([Web]). |
Belantamab mafodotin, an anti-B-cell maturation antigen (BCMA) antibody conjugated with the microtubule inhibitor monomethyl auristatin F (MMAF), is an antineoplastic agent.1
Belantamab mafodotin-blmf is used in combination with bortezomib and dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma who were administered at least 2 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.1 Belantamab mafodotin is designated an orphan drug by FDA for treatment of multiple myeloma.2
The efficacy of belantamab mafodotin in combination with bortezomib and dexamethasone in adults with relapsed or refractory multiple myeloma who received at least 1 line of therapy with documented disease progression during or after the most recent therapy was evaluated in the open-label, randomized DREAMM-7 study.1 One group of enrolled patients was randomly assigned to belantamab mafodotin 2.5 mg/kg IV every 3 weeks on Day 1 of each 21-day cycle with bortezomib 1.3 mg/m2 subcutaneously on Days 1, 4, 8, and 11 and dexamethasone 20 mg IV or orally on the day of, and the day after, bortezomib in cycles 1 to 8.1 From cycle 9 onward, belantamab mafodotin was administered as monotherapy.1 The other group was assigned combination therapy with daratumumab, bortezomib, and dexamethasone for cycles 1 to 8 with daratumumab monotherapy from cycle 9 onward.1 Treatment with belantamab mafodotin or daratumumab was continued until disease progression or unacceptable toxicity.1
A total of 217 patients who had received at least 2 prior lines of therapy, including a proteasome inhibitor and immunomodulatory agent, were evaluated for efficacy in DREAMM-7 based on progression-free survival and overall survival.1 The median age of enrolled patients was 65 years (range: 39‒86 years); 53% were male; 86% were White; 11% Asian; and 2% Black.1 Results revealed a median progression-free survival of 31.3 months in the belantamab mafodotin group compared to 10.4 months in the daratumumab group.1 Median overall survival was not reached in the belantamab mafodotin group and was 35.7 months in the daratumumab group.1 Belantamab mafodotin combination therapy was also associated with an improvement in the overall response rate (81.5% versus 56.9%).1
The American Society of Clinical Oncology (ASCO) and Ontario Health (Cancer Care Ontario) published evidence-based recommendations for the treatment of multiple myeloma, including those with relapsed or refractory disease.5 For the treatment of relapsed or refractory disease, the guideline recommends triplet therapy or T-cell redirecting therapies for eligible patients.5 Patients should be offered treatment regimens that include different agents from those in prior therapies whenever possible.5 The optimal sequencing of therapy is evolving and sequencing decisions should be made based on patient factors, disease characteristics, mechanism of action, and prior treatment responses.5
Procedures for proper handling (e.g., use of gloves and protective clothing) and disposal of antineoplastic agents should be followed.1
Belantamab mafodotin-blmf is administered by IV infusion over approximately 30 minutes.1 Use of an inline filter is optional; however, if an inline filter is used, the manufacturer states that a 0.2-µm polyethersulfone (PES) inline filter should be used.1
Belantamab mafodotin-blmf should not be mixed with or administered simultaneously through the same IV line with other drugs.1
Unopened vials of belantamab mafodotin-blmf lyophilized powder for injection should be stored at 2-8°C.1
Prior to administration, belantamab mafodotin-blmf lyophilized powder for injection must be reconstituted and diluted using proper aseptic technique.1 The appropriate number of vials containing belantamab mafodotin-blmf should be removed from the refrigerator and allowed to sit for approximately 10 minutes to reach room temperature (20-25°C).1 The powder for injection is reconstituted by adding 1.4 mL of sterile water for injection to a vial labeled as containing 70 mg of the drug to provide a solution containing 50 mg/mL.1 The vial should be gently swirled until complete dissolution occurs; the vial should not be shaken.1
The reconstituted solution should be inspected visually for particulate matter and discoloration prior to dilution; the reconstituted solution should be clear to opalescent, colorless to yellow to brown, and free of visible particulates.1 Reconstituted solutions may be diluted immediately or stored for up to 4 hours at 2-8°C or 20-25°C.1 The reconstituted solution should not be frozen.1
For preparation of the final diluted belantamab mafodotin-blmf solution for infusion, the required amount of reconstituted belantamab mafodotin-blmf solution should be injected into a polyvinylchloride (PVC) or polyolefin infusion bag containing 250 mL of 0.9% sodium chloride injection to produce a final concentration of 0.2-2 mg/mL.1 The final diluted belantamab mafodotin-blmf solution for infusion should be mixed by gentle inversion and should not be shaken.1 Prior to administration, the diluted solution should be inspected visually for particulate matter and discoloration.1 The diluted solution should be clear and colorless, and free of visible particulates.1 Final diluted belantamab mafodotin-blmf solutions for infusion may be administered immediately using an infusion set made of PVC or polyolefin or stored at 2-8°C for up to 24 hours.1 Diluted solutions of the drug should not be frozen.1 If refrigerated, allow the diluted solution to reach room temperature (20-25°C) prior to administration.1 The diluted solution for infusion should be administered within 6 hours (including infusion time) following removal from refrigeration.1 Any unused portions in the vial should be discarded.1
The dose of belantamab mafodotin-blmf should be calculated based on actual body weight.1 Multiple vials may be necessary for a full dose.1
For the treatment of relapsed or refractory multiple myeloma previously treated with at least 2 prior therapies, including a proteasome inhibitor and an immunomodulatory agent, the recommended adult dosage of belantamab mafodotin-blmf is 2.5 mg/kg administered as an IV infusion over approximately 30 minutes once every 3 weeks in combination with bortezomib and dexamethasone for the first 8 cycles.1 This is followed by belantamab mafodotin-blmf 2.5 mg/kg as an IV infusion once every 3 weeks as a single agent.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
For dosing instructions for bortezomib and dexamethasone, please refer to their individual prescribing information.1
Dosage Modification for Toxicity
If adverse reactions occur, temporary interruption of therapy, dosage reduction, and/or discontinuance of belantamab mafodotin may be necessary.1 If dosage reduction is necessary, an initial dosage reduction to 1.9 mg/kg once every 3 weeks is recommended.1 The belantamab mafodotin dose should be further reduced to 1.9 mg/kg every 8 weeks if ocular toxicity based on ophthalmic exam findings occurs.1 The belantamab mafodotin dose should not be reescalated after a dosage reduction is made for ocular toxicity based on ophthalmic exam findings.1
If ocular adverse effects occur, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug as described in Table 1 may be necessary.1
Severity | Findings | Dosage Modification |
|---|---|---|
Grade 1 | Corneal exam findings: Mild superficial punctate keratopathy and/or Change in best corrected visual acuity (BCVA): Decline from baseline of 1 line on Snellen Equivalent BCVA | Continue therapy at current dosage |
Grade 2 | Corneal exam findings: Moderate superficial punctate keratopathy, patchy microcyst-like deposits, peripheral sub-epithelial haze, or a new peripheral stromal opacity and/or Change in BCVA: Decline from baseline of 2 lines on Snellen Equivalent BCVA and not worse than 20/200 | Withhold therapy until improvement in both corneal exam findings and change in BCVA to Grade 1 or less. Resume treatment at reduced dosage of 1.9 mg/kg every 3 weeks. If recurrent Grade 2 or 3 ocular toxicity is experienced, resume treatment at reduced dosage of 1.9 mg/kg every 8 weeks. |
Grade 3 | Corneal exam findings: Severe superficial punctate keratopathy, diffuse microcyst-like deposits involving the central cornea, central sub-epithelial haze, or a new central stromal opacity and/or Change in BCVA: Decline from baseline of 3 or more lines on Snellen Equivalent BCVA and not worse than 20/200 | Withhold therapy until improvement in both corneal exam findings and change in BCVA to Grade 1 or less. Resume treatment at reduced dosage of 1.9 mg/kg every 3 weeks. If recurrent Grade 2 or 3 ocular toxicity is experienced, resume treatment at reduced dosage of 1.9 mg/kg every 8 weeks. |
Grade 4 | Corneal exam findings: Corneal epithelial defect or corneal ulcer, with or without infection and/or Change in BCVA: Decline to Snellen Equivalent BCVA of worse than 20/200 | Consider permanently discontinuing therapy. If continuing therapy, withhold until improvement in both corneal exam findings and change in BCVA to Grade 1 or less. For patients previously on 2.5 mg/kg every 3 weeks, resume treatment at reduced dosage of 1.9 mg/kg every 3 weeks. For patients previously on 1.9 mg/kg every 3 weeks, resume treatment at reduced dosage of 1.9 mg/kg every 8 weeks. If recurrent Grade 4 ocular toxicity occurs, permanently discontinue therapy. |
If a platelet count between 25,000 and 50,000/mm3 without bleeding occurs, reduce dosage to 1.9 mg/kg every 3 weeks for patients on 2.5 mg/kg.1 For patients on the 1.9 mg/kg dosage, continue at the same dosage.1 Consider reverting to previous dose if appropriate once platelet count recovers to ≥50,000/mm3.1
If a platelet count between 25,000 and 50,000/mm3 with bleeding occurs, withhold therapy until bleeding resolves.1 For patients who were previously on 2.5 mg/kg, resume therapy at 1.9 mg/kg every 3 weeks.1 For patients who were already on the 1.9 mg/kg dosage, resume at the same dosage.1
If a platelet count less than 25,000/mm3 occurs, belantamab mafodotin therapy should be withheld until platelet count recovers to ≥25,000/mm3.1 For patients who were previously on 2.5 mg/kg, resume therapy at 1.9 mg/kg every 3 weeks.1 For patients who were already on the 1.9 mg/kg dosage, resume at the same dosage.1
If grade 2 or 3 infusion-related reactions occur, the infusion should be interrupted and appropriate supportive therapy provided.1 Once the reaction has resolved to Grade 1 or less, the infusion may be resumed and the infusion rate should be reduced by 50%.1 Clinicians should consider premedication for subsequent infusions.1
If grade 4 infusion-related reactions occur, belantamab mafodotin should be permanently discontinued; appropriate emergency care should be provided if anaphylactic or life-threatening reactions occur.1
If other grade 3 adverse effects occur, belantamab mafodotin therapy should be withheld until the toxicity improves to Grade 1 or less.1 For patients who were previously on 2.5 mg/kg, resume therapy at 1.9 mg/kg every 3 weeks.1 For patients who were already on the 1.9 mg/kg dosage, resume at the same dosage.1
If grade 4 adverse reactions occur, permanent discontinuance of belantamab mafodotin therapy should be considered.1 If continuation of belantamab mafodotin therapy is desired, therapy should be withheld until the toxicity improves to Grade 1 or less.1 For patients who were previously on 2.5 mg/kg, resume therapy at 1.9 mg/kg every 3 weeks.1 For patients who were already on the 1.9 mg/kg dosage, resume at the same dosage.1
No dosage adjustment is necessary in patients with mild hepatic impairment (total bilirubin ≥ the upper limit of normal [ULN] to ≤1.5 times ULN and any AST, or total bilirubin ≤ULN with AST >ULN).1
The manufacturer states that an appropriate dosage for patients with moderate or severe hepatic impairment has not been established.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Belantamab mafodotin causes ocular toxicity (i.e., changes in the corneal epithelium and in best-corrected visual acuity [BCVA] based on ophthalmic exam, or other ocular adverse reactions); the prescribing information for belantamab mafodotin contains a boxed warning regarding this risk.1
In the DREAMM-7 study, ocular toxicity occurred in 92% of patients, including Grade 3 or 4 toxicity in 77% of patients.1 The most common ocular toxicities (>25%) included reduction in BCVA (89%) and corneal exam findings (86%) based on ophthalmic exam findings, blurred vision (66%), dry eye (51%), photophobia (47%), foreign body sensation in eyes (44%), eye irritation (43%), and eye pain (33%).1 Ocular toxicity based on ophthalmic exam findings was reported as Grade 2 in 9% of patients, Grade 3 in 56% of patients, and Grade 4 in 21% of patients.1 The median time to onset of the first Grade 2 to 4 ophthalmic exam findings was 43 days (range: 15 to 611 days) and the median duration of all Grade 2 to 4 ophthalmic exam findings was 85 days (range: 5 to 813 days).1 Patients experienced a median of 3 episodes (range: 1 to 11 episodes) of ocular toxicity based on ophthalmic exam findings.1
The most commonly reported corneal exam findings included superficial punctate keratopathy, microcyst-like deposits, epithelial changes, and haze.1 Cases of corneal ulcer, including cases with infection, have been reported and should be managed promptly by an eye care professional.1
A reduction in BCVA to 20/50 or worse in at least one eye occurred in 69% of patients, including 29% who experienced a change in BCVA to 20/100 or worse, and 12% who experienced a change in BCVA to 20/200 or worse.1 Ophthalmic exams should be conducted by an ophthalmologist or optometrist at baseline, before each dose of belantamab mafodotin, promptly for new or worsening symptoms, and as clinically indicated.1 A baseline exam should be performed within 4 weeks prior to the initial dose.1 Each follow-up exam should be performed within 10 days prior to the next planned dose.1 Withhold belantamab mafodotin until improvement in both corneal exam findings and change in BCVA to Grade 1 or less and resume at same or reduced dose or permanently discontinue based on severity.1
Patients should be counseled to promptly inform their clinician of any ocular symptoms.1 Patients should use preservative-free artificial tears at least 4 times a day starting with the first infusion and continuing until the end of treatment, and avoid wearing contact lenses for the duration of therapy.1 Bandage contact lenses may be used under the direction of an eye care professional.1 Changes in visual acuity may be associated with difficulty driving and reading.1 Patients should be counseled to use caution when driving or operating machinery.1
Because of the risk of ocular toxicity, belantamab mafodotin-blmf is available only through a restricted distribution program (Blenrep® REMS).1
Other Warnings and Precautions
Thrombocytopenia has been reported in patients receiving belantamab mafodotin therapy.1 In DREAMM7, thrombocytopenia of any grade was reported in 100% of patients.1 Grade 2, 3, and 4 thrombocytopenia occurred in 10%, 29%, and 45% of patients, respectively.1 Clinically significant bleeding occurred in 7% of patients with concomitant low platelet levels.1
Complete blood cell (CBC) counts should be assessed at baseline and periodically during belantamab mafodotin treatment as clinically indicated.1 Withhold or reduce the dose of belantamab mafodotin based on severity of thrombocytopenia.1
Fetal/Neonatal Morbidity and Mortality
Belantamab mafodotin may cause fetal harm because of the genotoxic component (monomethyl auristatin F [MMAF]) of the antibody-drug conjugate.1
The manufacturer states that females of reproductive potential should be advised to use effective contraception while receiving belantamab mafodotin therapy and for 4 months after the last dose.1 In addition, men with such female partners should be advised to use effective contraception while receiving belantamab mafodotin therapy and for 6 months after the last dose.1 Patients should be apprised of the potential hazard to the fetus if belantamab mafodotin is used during pregnancy.1
There is a potential for immunogenicity with belantamab mafodotin therapy.1 In clinical studies involving combination therapy, development of anti-belantamab mafodotin antibodies was detected in 15 of 515 patients receiving belantamab mafodotin-blmf; neutralizing antibodies to belantamab mafodotin were detected in 2 of these 15 patients.1
Belantamab mafodotin may cause fetal harm if administered to pregnant women based on its mechanism of action; however, there are no available data on use in pregnant women or in animals.1 Human immunoglobulin (IgG) may cross the placenta; therefore, belantamab-mafodotin has the potential to cross the placenta from the mother to the developing fetus.1
It is not known whether belantamab mafodotin is distributed into human milk.1 The effects of the drug on breast-fed infants or on the production of milk are unknown.1
Because of the potential for serious adverse reactions to belantamab mafodotin in breast-fed infants, women should be advised not to breast-feed while receiving the drug and for 3 months after the last dose.1
Females and Males of Reproductive Potential
Females of reproductive potential should have their pregnancy status verified prior to therapy initiation.1 Females of reproductive potential should be advised to use effective contraception while receiving belantamab mafodotin therapy and for 4 months after the last dose.1 In addition, males with such female partners should be advised to use effective contraception while receiving belantamab mafodotin therapy and for 6 months after the last dose.1
Based on animal studies, belantamab mafodotin may impair fertility in females and males.1 The effects were not reversible in male rats but were reversible in female rats.1
Safety and efficacy of belantamab mafodotin-blmf have not been established in pediatric patients.1
In DREAMM-7, 121 (50%) of 242 patients were ≥65 years of age and 37 (15%) were ≥75 years of age.1 No overall differences in safety were noted between patients ≥65 years of age and younger patients.1 There were an insufficient number of patients ≥65 years of age evaluated for efficacy in the DREAMM-7 study to determine if effectiveness of therapy differed from effectiveness in younger adults.1
Mild hepatic impairment (total bilirubin >ULN to ≤1.5 times ULN and any AST or total bilirubin ≤ULN with AST >ULN) did not have clinically important effects on the pharmacokinetics of belantamab mafodotin.1
The effects of moderate or severe hepatic impairment on the pharmacokinetics of belantamab mafodotin are unknown.1
No clinically significant differences in the pharmacokinetics of belantamab mafodotin were seen in patients with mild to severe renal impairment and kidney failure.1
Adverse effects reported in at least 20% of patients receiving belantamab mafodotin-blmf in combination with bortezomib and dexamethasone include BCVA reduction, corneal exam findings, blurred vision, dry eye, photophobia, foreign body sensation in eyes, eye irritation, upper respiratory tract infection, hepatototoxicity, eye pain, diarrhea, fatigue, pneumonia, cataract, and COVID-19.1
Grade 3 or 4 laboratory abnormalities reported in at least 10% of patients include decreased platelets, decreased lymphocytes, decreased neutrophils, increased gamma-glutamyl transferase, decreased white blood cells, and decreased hemoglobin.1
No formal drug interaction studies have been performed with belantamab mafodotin; however, the risk of clinically relevant drug interactions appears to be minimal.3
In vitro studies also indicate that the microtubule inhibitor MMAF is a substrate of organic anion transporting polypeptide (OATP) 1B1, OATP1B3, multidrug resistance-associated protein (MRP) 1, MRP2, MRP3, bile salt export pump (BSEP), and possibly P-glycoprotein (P-gp).1
In vitro studies indicate that cys-mcMMAF (the microtubule inhibitor and linker following release from the monoclonal antibody) is not a sensitive substrate of cytochrome P-450 (CYP) isoenzymes and does not inhibit or induce CYP isoenzymes.3
Belantamab mafodotin, an anti-B-cell maturation antigen (BCMA) antibody-drug conjugate, is an antineoplastic agent.1 The anti-BCMA antibody, an afucosylated humanized IgG1 monoclonal antibody (belantamab), is covalently linked to a cytotoxic microtubule inhibitor (monomethyl auristatin F [MMAF]) via a protease-resistant maleimidocaproyl linker.1 Approximately 4 molecules of MMAF are attached to each antibody molecule.1 The antibody portion of belantamab mafodotin binds specifically to BCMA (also known as CD269 or TNFRSF17), a tumor necrosis factor transmembrane protein that plays a key role in B-cell maturation.1, 9 Expression of BCMA is selectively induced during differentiation of B cells to plasma cells and is minimally expressed in naïve B cells and nonhematopoietic cells.9, 10 Following binding of the antibody portion of belantamab mafodotin to BCMA, the resultant complex is internalized by the cell.1 MMAF is released via proteolytic cleavage of the maleimidocaproyl linker and disrupts the intracellular microtubule network, resulting in cell cycle arrest and apoptosis.1 Belantamab mafodotin has demonstrated antitumor activity in multiple myeloma cells and tumor cell lysis through MMAF-induced apoptosis, antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP).1
Belantamab mafodotin exhibits dose-proportional pharmacokinetics.1 Peak plasma concentrations of the antibody-drug conjugate are observed at or shortly after the end of IV infusion, and peak plasma concentrations of cysteine maleimidocaproyl monomethyl auristatin F (cys-mcMMAF; the microtubule inhibitor and linker following release from the monoclonal antibody) are observed approximately 23 hours after IV infusion.1, 3 In vitro, cys-mcMMAF exhibits low binding to plasma proteins, and binding is concentration dependent.3 The antibody portion of the antibody-drug conjugate is expected to undergo proteolysis to small peptides and amino acids.1 Following IV administration of a single dose of cys-mcMMAF, approximately 18% was recovered in urine.3 Belantamab mafodotin clearance decreases over time (by about 22% following the first dose to steady state).1 The elimination half-life of the antibody-drug conjugate is 13 days after the first dose and 17 days at steady state.1
The pharmacokinetics of the antibody-drug conjugate do not appear to be affected substantially by age (32-89 years), sex, race (White or Black), or body weight (37-170 kg).1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Distribution of belantamab mafodotin-blmf is restricted.1
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IV infusion only | 70 mg | Blenrep® (available as a single-dose vial) | GlaxoSmithKline |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions July 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. GlaxoSmithKline. Blenrep® (belantamab mafodotin-blmf) for injection prescribing information. Research Triangle Park, NC; 2025 Oct.
2. Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. [Web]
3. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761158Orig1s000: Multi-discipline review. From FDA website [Web]
5. Hicks LK, Messersmith HJ, Hadidi SA, et al. Treatment of multiple myeloma: ASCO-Ontario Health (Cancer Care Ontario) living guideline. J Clin Oncol . 2026;1-28.
9. Becnel MR, Lee HC. The role of belantamab mafodotin for patients with relapsed and/or refractory multiple myeloma. Ther Adv Hematol . 2020; 11:2040620720979813. [PubMed 33403093][PubMedCentral]
10. Tai YT, Mayes PA, Acharya C et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood . 2014; 123:3128-38. [PubMed 24569262][PubMedCentral]
11. GlaxoSmithKline. BLENREP REMS (Risk Evaluation and Mitigation Strategy). From the Blenrep® REMS website. [Web]