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BLENREP is indicated in adults for the treatment of multiple myeloma:1

  • In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy; and
  • In combination with pomalidomide and dexamethasone in patients who have received at least one prior therapy including lenalidomide
Explore BLENREP MOA

BLENREP is the first licensed BCMA-ADC treatment for use in relapsed/refractory multiple myeloma in the UK1–5

BCMA expression in multiple myeloma

BLENREP offers two different treatment combinations

BLENREP ▼ (belantamab mafodotin) is an antibody-drug conjugate (ADC) that combines the targeting capabilities of monoclonal antibodies (mAbs) with the cell-killing action of cytotoxic drugs.1,6 The first licensed ADC therapy for multiple myeloma in the UK, BLENREP is administered by an intravenous infusion initiated at 30 minutes.1,6 (Please refer to the SPC for full administration guidance).

Please see the Dosing and administration page for more information

BLENREP works by binding to B-cell maturation antigen (BCMA) on the surface of multiple myeloma cells and delivering a cytotoxic payload to the cancer cells.1,6

BLENREP is the first licensed BCMA-ADC treatment for use in relapsed/refractory multiple myeloma in the UK1–5

BLENREP consists of a humanised, afucosylated IgG1 kappa mAb, engineered to target BCMA.1 The BLENREP mAb is linked to a cytotoxic payload: monomethyl auristatin F (MMAF).1

The mechanism of BLENREP is supported by the maleimidocaproyl (mc) linker, a protease-resistant attachment that connects MMAF to the mAb.7 The stability of this linker helps ensure that MMAF is only released upon internalisation into myeloma cells.7
 
BLENREP’s structure features the afucosylation in the IgG1 antibody, which enhances antibody-dependent cellular cytotoxicity (ADCC), aiding immune response activation alongside the ADC’s direct tumour-killing action.8,9

Image of the BLENREP molecule

BLENREP is engineered to target multiple myeloma in two ways:

1) Payload-dependent1

BLENREP delivers MMAF as its intracellular cytotoxic payload, an inhibitor of tubulin polymerisation, which disrupts the microtubule network essential for cell division and intracellular trafficking.1,10 By binding directly to tubulin, MMAF arrests the cell cycle in the G2/M phase, leading to mitotic catastrophe and subsequent apoptosis.10,11

2) Immune-mediated1

Apoptosis of these cancer cells causes the release of damage-associated molecular patterns (DAMPs), including calreticulin exposure, ATP secretion, and HMGB1 release.12,13 These signals are known as immunogenic cell death (ICD) markers. These signals facilitate immune system activation by exposing tumour-associated antigens.1,14 This primes dendritic cells, which process and present these antigens to T cells, enhancing the adaptive immune response.13
 
BLENREP also engages ADCC and antibody-dependent cellular phagocytosis (ADCP), mechanisms that rely on the Fc region of the mAb.10 Once the antibody binds to BCMA on the cell surface, immune effector cells, such as natural killer (NK) cells and macrophages, can bind to the afucosylated Fc region on the BLENREP antibody, facilitating immune-mediated cell killing via co-localisation with the myeloma cells.13,15 The fucose deficient Fc region allows for increased binding affinity of the immune effector cells.15,16
 
Watch the video below to learn more about the BLENREP mechanism of action.

BCMA expression in multiple myeloma

BCMA is a cell surface transmembrane glycoprotein present on myeloma cells, late-stage B cells, and plasma cells, with little to no expression on naïve and memory B cells.6,17–19
 
BCMA has two major agonist ligands: B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL), which are associated with plasma cell survival and proliferation.20,21
 
BCMA overexpression is linked to enhanced myeloma cell proliferation and survival, resistance to apoptosis, angiogenesis, and drug resistance.17,19,22 BCMA in its soluble form (sBCMA), is also associated with immune suppression and worsened clinical outcomes.17 The correlation between BCMA expression and disease progression, therefore makes it a relevant biomarker and therapeutic target in multiple myeloma.17

Why target BCMA in multiple myeloma?

BCMA expression is predominantly restricted to myeloma cells: This helps to minimise off-target engagement, as BCMA protein is minimally expressed in normal human tissues, including in critical organs such as the brain.6,17–19,23,24

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By targeting BCMA with an ADC, BLENREP offers a different therapeutic target for eligible patients with relapsed or refractory multiple myeloma after first relapse.25

BLENREP offers two different treatment combinations to meet your eligible adult patients' needs

Review clinical data on BVd from DREAMM-7

Review clinical data on BPd from DREAMM-8

Abbreviations

ADC, antibody-drug conjugate; ADCC, antibody-dependent cellular cytotoxicity; ADCP, antibody-dependent cellular phagocytosis; APRIL, a proliferation-inducing ligand; BAFF, B-cell activation factor; BCMA, B-cell maturation antigen; BPd, belantamab mafodotin, pomalidomide and dexamethasone; BVd, belantamab mafodotin, bortezomib, dexamethasone; DAMP, damage-associated molecular pattern; ICD, immunogenic cell death; mAb, monoclonal antibody; mc, maleimidocaproyl; MMAF, monomethyl auristatin F; NK, natural killer; sBCMA, soluble B-cell maturation antigen; SPC, Summary of Product Characteristics

References

  1. BLENREP. Summary of Product Characteristics. GlaxoSmithKline; 2025.
  2. Darzalex. Summary of Product Characteristics. Janssen-Cilag Ltd.
  3. Kyprolis. Summary of Product Characteristics. Amgen Ltd.
  4. Nexpovio. Summary of Product Characteristics. Menari Stemline UK Ltd.
  5. Revlimid. Summary of Product Characteristics. Bristol Myers Squib Pharma limited.
  6. Tai YT, Mayes PA, Acharya C, Zhong MY, Cea M, Cagnetta A, et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014 May 15;123(20):3128–38.
  7. Mckertish CM, Kayser V. Advances and limitations of antibody drug conjugates for cancer. Biomedicines. 2021 Jul 23;9(8):872.
  8. Pereira NA, Chan KF, Lin PC, Song Z. The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity. MAbs. 2018 Jul 4;10(5):693–711.
  9. Lassiter G, Bergeron C, Guedry R, Cucarola J, Kaye AM, Cornett EM, et al. Belantamab mafodotin to treat multiple myeloma: A comprehensive review of disease, drug efficacy and side effects. Curr Oncol. 2021 Jan 21;28(1):640–60.
  10. Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduct Target Ther. 2022 Mar 22;7(1):93.
  11. Nilchan N, Li X, Pedzisa L, Nanna AR, Roush WR, Rader C. Dual-mechanistic antibody-drug conjugate via site-specific selenocysteine/cysteine conjugation. Antib Ther. 2019 Oct 24;2(4):71–8.
  12. Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology. 2014 Oct 13;3(9):e955691.
  13. Zhou J, Wang G, Chen Y, Wang H, Hua Y, Cai Z. Immunogenic cell death in cancer therapy: Present and emerging inducers. J Cell Mol Med. 2019 Aug 18;23(8):4854–65.
  14. Mielnik M, Musa, H, Barnard R, et al. Belantamab mafodotin exhibits no evidence of immune cell impairment: potential implicationsfor sequencing therapies in multiple myeloma. Presented at: EHA 2024; 13-16 June 2024; Madrid, Spain.
  15. Morè S, Offidani M, Corvatta L, Petrucci MT, Fazio F. Belantamab Mafodotin: From clinical trials data to real-life experiences. Cancers (Basel). 2023 May 27;15(11):2948.
  16. Golay J, Andrea AE, Cattaneo I. Role of Fc core fucosylation in the effector function of IgG1 antibodies. Front Immunol. 2022 Jun 30;13:929895.
  17. Cohen AD. CAR T cells and other cellular therapies for multiple myeloma: 2018 update. Am Soc Clin Oncol Educ Book. 2018 May 23;38(38):e6–15.
  18. Lee L, Bounds D, Paterson J, Herledan G, Sully K, Seestaller-Wehr LM, et al. Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma. Br J Haematol. 2016 Sep;174(6):911–22.
  19. Seckinger A, Delgado JA, Moser S, Moreno L, Neuber B, Grab A, et al. Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment. Cancer Cell. 2017 Mar 13;31(3):396–410.
  20. Yu B, Jiang T, Liu D. BCMA-targeted immunotherapy for multiple myeloma. J Hematol Oncol. 2020 Sep 17;13(1):125.
  21. Cho SF, Anderson KC, Tai YT. Targeting B cell maturation antigen (BCMA) in multiple myeloma: Potential uses of BCMA-based immunotherapy. Front Immunol. 2018 Aug 10;9:1821.
  22. Tai YT, Acharya C, An G, Moschetta M, Zhong MY, Feng X, et al. APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood. 2016 Jun 23;127(25):3225–36.
  23. Marella M, Yao X, Carreira V, Bustamante MF, Clark HB, Jackson CC, et al. Comprehensive BCMA expression profiling in adult normal human brain suggests a low risk of on-target neurotoxicity in BCMA-targeting multiple myeloma therapy. J Histochem Cytochem. 2022 Apr 22;70(4):273–87.
  24. Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013 Apr 15;19(8):2048–60.
  25. Kleber M, Ntanasis-Stathopoulos I, Terpos E. BCMA in multiple myeloma - a promising key to therapy. J Clin Med 2021;10(18):4088.

▼This product is subject to additional monitoring. Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk or via the Yellow Card app (available on the Apple App Store or Google Play Store). Adverse events should also be reported to GlaxoSmithKline on 0800 221 441 or UKSafety@GSK.com.

October 2025 | PM-GB-BLM-WCNT-250002 (V1.0)