Belantamab mafodotin

Belantamab mafodotin
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetB-cell maturation antigen (BCMA) (CD269)
Clinical data
Trade namesBlenrep
Other namesGSK2857916, GSK-2857916, belantamab mafodotin-blmf
AHFS/Drugs.comMonograph
MedlinePlusa620052
License data
Routes of
administration		Intravenous
Drug classAntineoplastic agent
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
FormulaC6484H10038N1728O2026S44
Molar mass146026.34 g·mol−1

Belantamab mafodotin, sold under the brand name Blenrep, is a monoclonal antibody conjugated with a cytotoxic agent for the treatment of relapsed and refractory multiple myeloma.[3][8][9][4] Belantamab mafodotin is a B-cell maturation antigen (BCMA)-directed antibody and microtubule inhibitor conjugate.[3]

The most common adverse reactions include keratopathy (corneal epithelium change on eye exam), decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, and fatigue.[3][8]

Belantamab mafodotin is a humanized IgG1κ monoclonal antibody against the B-cell maturation antigen (BCMA) conjugated with a cytotoxic agent, maleimidocaproyl monomethyl auristatin F (mcMMAF).[4] The antibody-drug conjugate binds to BCMA on myeloma cell surfaces causing cell cycle arrest and inducing antibody-dependent cellular cytotoxicity.[4]

Belantamab mafodotin was approved for medical use in the United States and in the European Union in August 2020.[8][9][4] The US Food and Drug Administration considers it to be a first-in-class medication.[10][11]

Medical uses

In the EU, belantamab mafodotin is indicated for the treatment of adults with relapsed or refractory multiple myeloma: in combination with bortezomib and dexamethasone in people who have received at least one prior therapy; and in combination with pomalidomide and dexamethasone in people who have received at least one prior therapy including lenalidomide.[4]

In the US, belantamab mafodotin is indicated for use in combination with bortezomib and dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.[3]

Adverse effects

The US prescribing information includes a boxed warning stating belantamab mafodotin causes changes in the corneal epithelium resulting in alterations in vision, including severe vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eyes.[8][3] Among those receiving belantamab mafodotin in DREAMM-7, ocular toxicity occurred in 92% of participants, including grade 3 or 4 in 77%, with 83% requiring dosage modification due to ocular toxicity.[12] Because of the risk of ocular toxicity, belantamab mafodotin is available in the US only through a risk evaluation and mitigation strategy (REMS), called the BLENREP REMS.[12] Other warnings and precautions include thrombocytopenia and embryo-fetal toxicity.[12]

History

Belantamab mafodotin was evaluated in DREAMM-2 (NCT03525678), an open-label, multi-center trial.[8] Participants received either belantamab mafodotin, 2.5 mg/kg or 3.4 mg/kg intravenously, once every three weeks until disease progression or unacceptable toxicity.[8]

Efficacy was based on overall response rate (ORR) and response duration, as evaluated by an independent review committee using the International Myeloma Working Group uniform response criteria.[8] The ORR was 31% (97.5% CI: 21%, 43%). Seventy-three percent of responders had response durations ≥6 months.[8] These results were observed in participants receiving the recommended dose of 2.5 mg/kg.[8]

The US Food and Drug Administration (FDA) granted the application for belantamab mafodotin priority review, orphan drug, and breakthrough therapy designations.[8]

In 2023, the confirmatory phase III DREAMM-3 trial aimed to compare belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in participants with relapsed or refractory multiple myeloma. Due to the trial results, the manufacturer is voluntarily withdrawing belantamab mafodotin from the market.[13]

The efficacy of belantamab mafodotin with bortezomib and dexamethasone was evaluated in DREAMM-7 (NCT04246047), an open-label, randomized, multi-center trial in adults with relapsed or refractory multiple myeloma who had received at least one line of prior therapy.[12] The trial excluded people who were refractory or intolerant to daratumumab or bortezomib, had received prior B-cell maturation antigen-directed therapy, and had existing corneal disease, except for mild punctate keratopathy.[12]

Society and culture

Belantamab mafodotin was approved for medical use in the United States and in the European Union in August 2020.[8][9][4][11]

Belantamab mafodotin was withdrawn in the United States[14] and the European Union.[4] In November 2022, GSK initiated the process for withdrawal of the United States marketing authorization for belantamab mafodotin following the request of the US Food and Drug Administration (FDA).[15] This request was based on the outcome of the DREAMM-3 phase III confirmatory trial,[13] which did not meet the requirements of the US FDA accelerated approval regulations.[16]

In May 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Blenrep, intended for the treatment of relapsed or refractory multiple myeloma.[6] The applicant for this medicinal product is GlaxoSmithKline Trading Services Limited.[6] Blenrep was reauthorized for medical use in the European Union in July 2025.[6][7]

Belantamab mafodotin was reapproved for medical use in the United States in October 2025.[12]

Names

Belantamab mafodotin is the international nonproprietary name (INN).[17]

References

  1. ^ "Blenrep Product information". Health Canada. 11 August 2025. Retrieved 24 October 2025.
  2. ^ "Blenrep Product information". Health Canada. 11 August 2025. Retrieved 24 October 2025.
  3. ^ a b c d e f https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761440s000lbl.pdf
  4. ^ a b c d e f g h "Blenrep EPAR". European Medicines Agency (EMA). 23 July 2020. Archived from the original on 1 November 2020. Retrieved 24 September 2020.
  5. ^ "Blenrep Product information". Union Register of medicinal products. Archived from the original on 5 March 2023. Retrieved 3 March 2023.
  6. ^ a b c d "Blenrep EPAR". European Medicines Agency (EMA). 23 May 2025. Retrieved 15 June 2025. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. ^ a b "Blenrep PI". Union Register of medicinal products. 24 July 2025. Retrieved 31 July 2025.
  8. ^ a b c d e f g h i j k "FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma". U.S. Food and Drug Administration (FDA). 5 August 2020. Archived from the original on 6 August 2020. Retrieved 6 August 2020. This article incorporates text from this source, which is in the public domain.
  9. ^ a b c "FDA Approves GSK's Blenrep (belantamab mafodotin-blmf) for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma" (Press release). GlaxoSmithKline. 6 August 2020. Archived from the original on 6 August 2020. Retrieved 6 August 2020 – via Business Wire.
  10. ^ "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Archived from the original on 18 January 2021. Retrieved 17 January 2021.
  11. ^ a b "Drug Approval Package: Blenrep". U.S. Food and Drug Administration (FDA). 1 August 2020. Archived from the original on 21 January 2021. Retrieved 17 January 2021.
  12. ^ a b c d e f "FDA approves belantamab mafodotin-blmf for relapsed or refractory multiple myeloma". U.S. Food and Drug Administration (FDA). 23 October 2025. Retrieved 23 October 2025. This article incorporates text from this source, which is in the public domain.
  13. ^ a b "GSK provides update on DREAMM-3 phase III trial for Blenrep in relapsed/refractory multiple myeloma" (Press release). GSK. 11 July 2022. Archived from the original on 23 November 2022. Retrieved 23 November 2022.
  14. ^ "FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma". U.S. Food and Drug Administration. 20 March 2023. Archived from the original on 15 August 2024. Retrieved 15 August 2024.
  15. ^ "GSK provides an update on Blenrep (belantamab mafodotin-blmf) US marketing authorization" (Press release). GSK. 22 November 2022. Archived from the original on 23 November 2022. Retrieved 23 November 2022.
  16. ^ "GlaxoSmithKline Intellectual Property Development Ltd. England; Announcement of the Revocation of the Biologics License for Blenrep". Federal Register. 30 March 2023. Archived from the original on 30 March 2023. Retrieved 15 August 2024.
  17. ^ World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 80". WHO Drug Information. 32 (3): 431–2. hdl:10665/330907. License: CC BY-NC-SA 3.0 IGO.

Further reading

  • "Belantamab mafodotin". NCI Drug Dictionary. National Cancer Institute.
  • "Belantamab Mafodotin ( Code - C114299 )". EVS Explore.
  • Clinical trial number NCT03525678 for "A Study to Investigate the Efficacy and Safety of Two Doses of GSK2857916 in Participants With Multiple Myeloma Who Have Failed Prior Treatment With an Anti-CD38 Antibody" at ClinicalTrials.gov
  • Clinical trial number NCT04246047 for "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)" at ClinicalTrials.gov
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