Belantamab mafodotin

Belantamab mafodotin

Monoclonal antibody
Type	Whole antibody
Source	Humanized
Target	B-cell maturation antigen (BCMA) (CD269)
Clinical data
Trade names	Blenrep
Other names	belantamab mafodotin-blmf, GSK2857916
AHFS/Drugs.com	Monograph
License data	US DailyMed: Belantamab_mafodotin
Routes of administration	Intravenous
Drug class	Antineoplastic agent
ATC code	L01FX15 (WHO)
Legal status
Legal status	US: ℞-only EU: Rx-only
Identifiers
CAS Number	2050232-20-5 Y
DrugBank	DB15719
UNII	DB1041CXDG
KEGG	D11595
Chemical and physical data
Formula	C6484H10008N1728O2030S44. (C49H66N6O11)4

Belantamab mafodotin, sold under the brand name Blenrep, is a medication for the treatment of relapsed and refractory multiple myeloma.

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.

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). The antibody-drug conjugate binds to BCMA on myeloma cell surfaces causing cell cycle arrest and inducing antibody-dependent cellular cytotoxicity.

Belantamab mafodotin was approved for medical use in the United States and in the European Union in August 2020. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.

On November 22, 2022, GSK plc announced it initiated the process for withdrawal of the United States marketing authorization for belantamab mafodotin following the request of the U.S. FDA. This request was based on the outcome of the DREAMM-3 phase III confirmatory trial, which did not meet the requirements of the U.S. FDA Accelerated Approval regulations.

Medical uses

Belantamab mafodotin is indicated for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.

Adverse effects

The 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.

Because of the risks of ocular toxicity, belantamab mafodotin is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the BLENREP REMS.

History

Belantamab mafodotin was evaluated in DREAMM-2 (NCT 03525678), an open-label, multicenter trial. 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.

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. The ORR was 31% (97.5% CI: 21%, 43%). Seventy-three percent of responders had response durations ≥6 months. These results were observed in participants receiving the recommended dose of 2.5 mg/kg.

The U.S. Food and Drug Administration (FDA) granted the application for belantamab mafodotin priority review, orphan drug designation, and breakthrough therapy designation.

Society and culture

Legal status

Belantamab mafodotin was approved for medical use in the United States and in the European Union in August 2020.

Names

Belantamab mafodotin is the international nonproprietary name (INN).

Further reading

• Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, et al. (March 2019). "Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study". Blood Cancer J. 9 (4): 37. doi:10.1038/s41408-019-0196-6. PMC 6426965. PMID 30894515.
• Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. (February 2020). "Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study". Lancet Oncol. 21 (2): 207–221. doi:10.1016/S1470-2045(19)30788-0. PMID 31859245. S2CID 209425201.

External links

• "Belantamab mafodotin". Drug Information Portal. U.S. National Library of Medicine.
• "Belantamab mafodotin". NCI Drug Dictionary. National Cancer Institute.
• 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