Belantamab Mafodotin: First Approval

Published on Oct 1, 2020in Drugs6.189
· DOI :10.1007/S40265-020-01404-X
Anthony Markham20
Estimated H-index: 20
(Springer Science+Business Media)
Belantamab mafodotin (BLENREP™; belantamab mafodotin-blmf) is a first-in-class monoclonal antibody-drug conjugate (ADC) that has been developed for the treatment of multiple myeloma by GlaxoSmithKline. The ADC comprises an antibody targeting B-cell maturation antigen (BCMA) conjugated to the microtubule inhibitor monomethyl auristatin F (MMAF). The antibody moiety binds to BCMA on the tumour cell surface, delivering the cytotoxic microtubule inhibitor MMAF to the therapeutic target. Based on preliminary results from the multinational DREAMM-2 trial, belantamab mafodotin was approved in early August 2020 in the USA for the treatment of relapsed or refractory multiple myeloma in adult patients who have received at least four prior therapies, including an anti CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. The ADC was also approved in the EU for this indication in late August 2020. This article summarizes the milestones in the development of belantamab mafodotin leading to this first approval.
📖 Papers frequently viewed together
22 Citations
10 Citations
16 Citations
#2Chetan RathiH-Index: 8
Last. Roxanne C. JewellH-Index: 13
view all 6 authors...
Background: Belantamab mafodotin (GSK2857916) is a first-in-class B-cell maturation antigen (BCMA)-targeting immunoconjugate with a humanized afucosylated anti-BCMA mAb conjugated to a cytotoxic payload mafodotin (MMAF) by a protease-resistant maleimidocaproyl linker (mc). This antibody-drug conjugate (ADC) binds to BCMA and eliminates MM cells by a multimodal mechanism. It delivers MMAF to MM cells which inhibits microtubule polymerization, resulting in apoptosis, enhances antibody-dependent ce...
4 CitationsSource
#1Sagar Lonial (Emory University Hospital)H-Index: 99
#2Hans C. Lee (University of Texas MD Anderson Cancer Center)H-Index: 15
Last. Adam D. Cohen (UPenn: University of Pennsylvania)H-Index: 51
view all 20 authors...
8536Background: Single-agent belantamab mafodotin (B-cell maturation antigen targeting immunoconjugate) showed clinically meaningful activity and manageable safety in patients with heavily pre-trea...
19 CitationsSource
#1Saad Z. UsmaniH-Index: 55
#2Evangelos Terpos (UoA: National and Kapodistrian University of Athens)H-Index: 85
Last. Ira Gupta (GSK: GlaxoSmithKline)H-Index: 17
view all 10 authors...
TPS8556Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is the standard of care for transplant-eligible and TI NDMM, but relapse is usually inevitable. The median progression-free surv...
7 CitationsSource
#1Paul G. Richardson (Harvard University)H-Index: 207
#2Swethajit Biswas (GSK: GlaxoSmithKline)H-Index: 2
Last. Katarina Luptakova (GSK: GlaxoSmithKline)H-Index: 3
view all 16 authors...
TPS8552Background: Single-agent belantamab mafodotin (GSK2857916), a B-cell maturation antigen targeting immunoconjugate, induced deep and durable responses in patients with RRMM, with a manageable...
6 CitationsSource
#1Sagar Lonial (Emory University)H-Index: 99
#2Hans C. Lee (University of Texas MD Anderson Cancer Center)H-Index: 15
Last. Adam D. CohenH-Index: 51
view all 38 authors...
Summary Background Belantamab mafodotin (GSK2857916), an immunoconjugate targeting B-cell maturation antigen, showed single-agent activity in the phase 1 DREAMM-1 study in heavily pre-treated patients with relapsed or refractory multiple myeloma. We further investigated the safety and activity of belantamab mafodotin in the DREAMM-2 study. Methods DREAMM-2 is an open-label, two-arm, phase 2 study done at 58 multiple myeloma specialty centres in eight countries. Patients (aged ≥18 years) with rel...
201 CitationsSource
#1Suzanne Trudel (Princess Margaret Cancer Centre)H-Index: 27
#2Nikoletta Lendvai (Cornell University)H-Index: 19
Last. Adam D. Cohen (UPenn: University of Pennsylvania)H-Index: 51
view all 13 authors...
Interim analyses of a phase I study with GSK2857916, an antibody–drug conjugate against B cell maturation antigen, have previously reported a 60% overall response and 7.9 months progression-free survival in relapsed/refractory multiple myeloma (MM). We provide updated safety and efficacy results of the BMA117159 trial following an additional 14 months' follow-up. This open-label, first-in-human, phase I study was conducted at nine centres in the USA, Canada and the UK, and included adults with M...
110 CitationsSource
#1Yu-Tzu Tai (Harvard University)H-Index: 89
#2Patrick A. Mayes (GSK: GlaxoSmithKline)H-Index: 8
Last. Kenneth C. Anderson (Harvard University)H-Index: 211
view all 17 authors...
B-cell maturation antigen (BCMA), highly expressed on malignant plasma cells in human multiple myeloma (MM), has not been effectively targeted with therapeutic monoclonal antibodies. We here show that BCMA is universally expressed on the MM cell surface and determine specific anti-MM activity of J6M0-mcMMAF (GSK2857916), a novel humanized and afucosylated antagonistic anti-BCMA antibody-drug conjugate via a noncleavable linker. J6M0-mcMMAF specifically blocks cell growth via G2/M arrest and indu...
259 CitationsSource
Cited By25
#1Juliana T. W. TongH-Index: 1
#2Paul W. R. HarrisH-Index: 18
Last. Iman KavianiniaH-Index: 9
view all 4 authors...
The large number of emerging antibody-drug conjugates (ADCs) for cancer therapy has resulted in a significant market ‘boom’, garnering worldwide attention. Despite ADCs presenting huge challenges to researchers, particularly regarding the identification of a suitable combination of antibody, linker, and payload, as of September 2021, 11 ADCs have been granted FDA approval, with eight of these approved since 2017 alone. Optimism for this therapeutic approach is clear, despite the COVID-19 pandemi...
#1Neret Pujol-Navarro (Strathclyde Institute of Pharmacy and Biomedical Sciences)
#2Mohammed M. Al Qaraghuli (Strathclyde Institute of Pharmacy and Biomedical Sciences)H-Index: 7
Last. Paul A. Mulheran (University of Strathclyde)H-Index: 21
view all 10 authors...
Multiple myeloma is the second most common hematological malignancy in adults, accounting for 2% of all cancer-related deaths in the UK. Current chemotherapy-based regimes are insufficient, as most patients relapse and develop therapy resistance. This review focuses on current novel antibody- and aptamer-based therapies aiming to overcome current therapy limitations, as well as their respective limitations and areas of improvement. The use of computer modeling methods, as a tool to study and imp...
Multiple myeloma is an incurable disease of malignant plasma cells and an ideal target for modern immune therapy. The unique plasma cell biology maintained in multiple myeloma, coupled with its hematological nature and unique bone marrow microenvironment, provide an opportunity to design specifically targeted immunotherapies that selectively kill transformed cells with limited on-target off-tumor effects. Broadly defined, immune therapy is the utilization of the immune system and immune agents t...
#1Dian XiaoH-Index: 3
Last. Xinbo ZhouH-Index: 4
view all 8 authors...
Abstract null null In recent years, tumor immunotherapy, especially the combination of PD1/PD-L1 inhibitors and chemotherapy, has developed rapidly. However, the systemic side effects induced by chemotherapy remain a crucial problem that needs to be addressed. Antibody drug conjugates (ADCs) are exceptional target-specific prodrugs that greatly improve the therapeutic window of chemotherapy drugs. Therefore, designing PD-L1-targeting ADCs is an interesting research project. In this study, we con...
#1Faiza Javaid (UCL Institute of Ophthalmology)
#7James R. BakerH-Index: 86
Last. Vijay ChudasamaH-Index: 30
view all 10 authors...
#1Iris Katariina Sokka (UH: University of Helsinki)H-Index: 1
#2Surachet Imlimthan (UH: University of Helsinki)H-Index: 3
Last. Filip S. Ekholm (UH: University of Helsinki)H-Index: 11
view all 6 authors...
Halogenation can be utilized for the purposes of labeling and molecular imaging, providing a means to, e.g., follow drug distribution in an organism through positron emission tomography (PET) or study the molecular recognition events unfolding by nuclear magnetic resonance (NMR) spectroscopy. For cancer therapeutics, where often highly toxic substances are employed, it is of importance to be able to track the distribution of the drugs and their metabolites in order to ensure minimal side effects...
#1Tommaso Tedeschini (UNIPD: University of Padua)H-Index: 1
#2B. Campara (UNIPD: University of Padua)
Last. Gianfranco Pasut (UNIPD: University of Padua)H-Index: 35
view all 9 authors...
Antibody-drug conjugates (ADCs) are an established therapeutic entity in which potent cytotoxic drugs are conjugated to a monoclonal antibody. In parallel with the great emphasis put on novel site-specific bioconjugation technologies, future advancements in this field also rely on exploring novel linker-drug architectures that improve the efficacy and stability of ADCs. In this context, the use of hydrophilic linkers represents a valid strategy to mask or reduce the inherent hydrophobicity of th...
1 CitationsSource
#1Hangping Yao (ZJU: Zhejiang University)H-Index: 28
#2Hui Zhao (WHU: Wuhan University)
Last. Ming-Hai Wang (TTUHSC: Texas Tech University Health Sciences Center)H-Index: 21
view all 5 authors...
Abstract null null Duocarmycins are a class of DNA minor-groove-binding alkylating molecules. For the past decade, various duocarmycin analogues have been used as payloads in the development of antibody–drug conjugates (ADCs). Currently, more than 15 duocarmycin-based ADCs have been studied preclinically, and some of them such as SYD985 have been granted Fast-Track Designation status. Nevertheless, progress in duocarmycin-based ADCs also faces challenges, with setbacks including the termination ...
#1Karun Neupane (Manipal College of Medical Sciences)H-Index: 2
#2Ahsan Wahab (UAB: University of Alabama at Birmingham)H-Index: 7
Last. Faiz Anwer (Cleveland Clinic)H-Index: 13
view all 8 authors...
Treatment options are limited for multiple myeloma patients who have developed four/five drug-refractory disease. Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of RRMM. The toxicity profile of these drugs is a concern since these agents are used in patients who have already undergone multiple lines of treatment. In this review, we discuss the toxicity profile and strategies for the management of toxicities of Sel and belamaf for the treatme...
#1Wenqian Li (JLU: Jilin University)H-Index: 4
#2Hanfei Guo (JLU: Jilin University)H-Index: 1
Last. Jiuwei Cui (JLU: Jilin University)H-Index: 29
view all 5 authors...
Introduction null Traditional cancer therapy has many disadvantages such as low selectivity and high toxicity of chemotherapy, as well as insufficient efficacy of targeted therapy. To enhance the cytotoxic effect and targeting ability, while reducing the toxicity of antitumor drugs, an antibody drug conjugate (ADC) was developed to deliver small molecular cytotoxic payloads directly to tumor cells by binding to specific antibodies via linkers. null Method null By reviewing published literature a...
1 CitationsSource