Belantamab mafodotin explained

Type:	mab
Mab Type:	mab
Source:	zu
Target:	B-cell maturation antigen (BCMA) (CD269)
Tradename:	Blenrep
Dailymedid:	Belantamab mafodotin
Routes Of Administration:	Intravenous
Class:	Antineoplastic agent
Atc Prefix:	L01
Atc Suffix:	FX15
Legal Us:	Rx-only
Legal Eu:	Rx-only
Legal Eu Comment:	^[1]
Cas Number:	2050232-20-5
Drugbank:	DB15719
Unii:	DB1041CXDG
Kegg:	D11595
Synonyms:	belantamab mafodotin-blmf, GSK2857916
Chemical Formula:	C6484H10008N1728O2030S44. (C49H66N6O11)4

Belantamab mafodotin, sold under the brand name Blenrep, is a monoclonal antibody for the treatment of relapsed and refractory multiple myeloma.^{[2] [3] [4]}

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.^[5] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.^{[6] [7]}

In November 2022, GSK plc initiated the process for withdrawal of the United States marketing authorization for belantamab mafodotin following the request of the US FDA.^[8] This request was based on the outcome of the DREAMM-3 phase III confirmatory trial,^[9] which did not meet the requirements of the US FDA accelerated approval regulations.^[10]

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. However, the phase III DREAMM-3 trial published in 2023, comparing patients with relapsed or refractory multiple myeloma receiving belantamab mafodotin to pomalidimide and dexamethasone did not demonstrate a clinical benefit for belantamab mafodotin. Due to this trial results, the manufacturer is voluntarily withdrawing belantamab mafodotin from the market.

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.

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

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.

Society and culture

Legal status

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

Belantamab mafodotin is withdrawn in the United States^[11] and the European Union.

Names

Belantamab mafodotin is the international nonproprietary name (INN).^[12]

Further reading

• Dimopoulos MA, Hungria VT, Radinoff A, Delimpasi S, Mikala G, Masszi T, Li J, Capra M, Maiolino A, Pappa V, Chraniuk D, Osipov I, Leleu X, Low M, Matsumoto M, Sule N, Li M, McKeown A, He W, Bright S, Currie B, Perera S, Boyle J, Roy-Ghanta S, Opalinska J, Weisel K . Efficacy and safety of single-agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-3): a phase 3, open-label, randomised study . The Lancet. Haematology . 10 . 10 . e801–e812 . October 2023 . 37793771 . 10.1016/S2352-3026(23)00243-0 .
• Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Lendvai N, Sborov D, Suvannasankha A, Weisel K, Karlin L, Libby E, Arnulf B, Facon T, Hulin C, Kortüm KM, Rodríguez-Otero P, Usmani SZ, Hari P, Baz R, Quach H, Moreau P, Voorhees PM, Gupta I, Hoos A, Zhi E, Baron J, Piontek T, Lewis E, Jewell RC, Dettman EJ, Popat R, Esposti SD, Opalinska J, Richardson P, Cohen AD . Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study . The Lancet. Oncology. 21 . 2 . 207–221 . February 2020 . 31859245 . 10.1016/S1470-2045(19)30788-0 . 209425201 .
• Morè S, Offidani M, Corvatta L, Petrucci MT, Fazio F . Belantamab Mafodotin: From Clinical Trials Data to Real-Life Experiences . Cancers . 15 . 11 . May 2023 . 2948 . 37296910 . 10251850 . 10.3390/cancers15112948 . free .
• Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Hoos A, Gupta I, Bragulat V, He Z, Opalinska JB, Cohen AD . 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 . March 2019 . 30894515 . 6426965 . 10.1038/s41408-019-0196-6 . free.

External links

• Web site: Belantamab mafodotin . NCI Drug Dictionary . National Cancer Institute .

Notes and References

1. Web site: Blenrep Product information . Union Register of medicinal products . 3 March 2023 . 5 March 2023 . https://web.archive.org/web/20230305055112/https://ec.europa.eu/health/documents/community-register/html/h1474.htm . live .
2. Web site: Blenrep- belantamab injection, powder, lyophilized, for solution . DailyMed . 5 August 2020 . 11 August 2020 . 27 October 2020 . https://web.archive.org/web/20201027200756/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=16a160a4-3ec0-4ddf-99ce-05912dd3382d . live .
3. Web site: FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma . U.S. Food and Drug Administration (FDA) . 5 August 2020 . 6 August 2020 . 6 August 2020 . https://web.archive.org/web/20200806201200/https://www.fda.gov/drugs/drug-approvals-and-databases/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma . live .
4. FDA Approves GSK's Blenrep (belantamab mafodotin-blmf) for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma . GlaxoSmithKline . Business Wire . 6 August 2020 . 6 August 2020 . 6 August 2020 . https://web.archive.org/web/20200806220236/https://www.businesswire.com/news/home/20200805006105/en/ . live .
5. Web site: Blenrep EPAR . European Medicines Agency (EMA) . 23 July 2020 . 24 September 2020 . 1 November 2020 . https://web.archive.org/web/20201101042614/https://www.ema.europa.eu/en/medicines/human/EPAR/blenrep . live .
6. Web site: New Drug Therapy Approvals 2020 . U.S. Food and Drug Administration (FDA) . 31 December 2020 . 17 January 2021 . 18 January 2021 . https://web.archive.org/web/20210118011953/https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2020 . live .
7. Web site: Drug Approval Package: Blenrep . U.S. Food and Drug Administration (FDA) . 1 August 2020 . 17 January 2021 . 21 January 2021 . https://web.archive.org/web/20210121021303/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/761158Orig1s000TOC.cfm . live .
8. GSK provides an update on Blenrep (belantamab mafodotin-blmf) US marketing authorization . 22 November 2022 . GSK . 23 November 2022 . 23 November 2022 . https://web.archive.org/web/20221123030125/https://us.gsk.com/en-us/media/press-releases/gsk-provides-an-update-on-blenrep-belantamab-mafodotin-blmf-us-marketing-authorization/ . live .
9. GSK provides update on DREAMM-3 phase III trial for Blenrep in relapsed/refractory multiple myeloma . 11 July 2022 . GSK . 23 November 2022 . 23 November 2022 . https://web.archive.org/web/20221123030125/https://www.gsk.com/en-gb/media/press-releases/gsk-provides-update-on-dreamm-3-phase-iii-trial-for-blenrep/ . live .
10. Web site: GlaxoSmithKline Intellectual Property Development Ltd. England; Announcement of the Revocation of the Biologics License for Blenrep . Federal Register . 30 March 2023 . 15 August 2024 . 30 March 2023 . https://web.archive.org/web/20230330120443/https://www.federalregister.gov/documents/2023/03/30/2023-06576/glaxosmithkline-intellectual-property-development-ltd-england-announcement-of-the-revocation-of-the . live .
11. Web site: FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma . U.S. Food and Drug Administration . 20 March 2023 . 15 August 2024 . 15 August 2024 . https://web.archive.org/web/20240815053235/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma . live .
12. ((World Health Organization)) . 2018 . International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 80 . WHO Drug Information . 32 . 3 . 431–2 . 10665/330907 . free . License: CC BY-NC-SA 3.0 IGO .