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Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Developed by GlaxoSmithKline, belantamab mafodotin (Figure 7.38) is a first-in-class anti-BCMA ADC designed for the treatment of adult patients with relapsed or refractory multiple myeloma. It consists of an anti-BCMA monoclonal antibody joined to the tubulin inhibiting auristatin F payload (MMAF) through a cleavable peptidic linker. It was approved by the FDA in 2020 as a monotherapy to treat adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies. Structure of belantamab mafodotin (Blenrep™) which consists of an anti-BCMA monoclonal antibody joined to the tubulin inhibiting auristatin F payload (MMAF) through a cleavable peptidic linker.
Elranatamab: a new promising BispAb in multiple myeloma treatment
Published in Expert Review of Anticancer Therapy, 2023
Sebastian Grosicki, Martyna Bednarczyk, Karolina Kociszewska
Previous studies regarding the first-in-class BCMA-targeted monoclonal antibody – belantamab mafodotin (humanized IgG1 monoclonal anti-BCMA antibody conjugated to the microtubule-disrupting agent monomethyl auristatin-F (MMAF)) proved its efficacy with relatively favorable safety profile [10,11]. It is approved in monotherapy for patients with relapsed/refractory multiple myeloma who have received ≥ 4 prior therapies [11]. The mechanism underneath is death of plasma cells with subsequent internalization and release of cytotoxic complex (cys-mcMMAF). A clinical trial called DREAMM-1 (phase 1) demonstrated its excellent single-agent activity at a dose of 3.4 mg/kg with an overall response rate (ORR) of 60% and a median PFS of 12 months in heavily pre-treated and refractory MM patients [1]. Previous research proved enhanced anti-MM acitivity when belantamab mafodotin is combined with other agents. Thus, belantamab mafodotin monotherapy could be insufficient [11].
Nonselective proteasome inhibitors in multiple myeloma and future perspectives
Published in Expert Opinion on Pharmacotherapy, 2022
Maria Gavriatopoulou, Panagiotis Malandrakis, Ioannis Ntanasis-Stathopoulos, Meletios Athanasios Dimopoulos
Proteasome inhibitors constitute the backbone of myeloma therapeutics. However, novel immunotherapies and nonimmune mediated approaches have revolutionized the treatment armamentarium especially in the relapsed/refractory setting such as chimeric antigen receptor (CAR) T-cells and bispecific antibodies. A better understanding of the immune microenvironment in myeloma has pinpointed the B-cell maturation antigen (BMCA) as a druggable target. In this context, BCMA-targeted treatments are being evaluated in late-phase clinical trials including CAR T-cells, antibody-drug conjugates (ADCs) and bispecific T cell engagers (BiTEs) [139]. Belantamab mafodotin, a BCMA-directed ADC, has gained regulatory approval for patients with RRMM recently. Other, non-immunotherapeutic agents with important anti-myeloma activity include the exportin inhibitor selinexor and the peptide-conjugated alkylator melflufen [4,140]. Although all these agents are particularly useful in heavily pre-treated patients who maybe refractory to prior therapy with PIs, their application in early lines of treatment may not be easy. These novel agents present a unique toxicity profile that may necessitate expert care, such as cytokine release syndrome and neurotoxicity with CAR T-cells and BiTEs or ocular toxicity with belantamab mafodotin. On the contrary, the toxicity profile of the proteasome inhibitors is well documented and manageable in the current clinical practice.
Antibodies to watch in 2021
Published in mAbs, 2021
Hélène Kaplon, Janice M. Reichert
On August 5, 2020, Blenrep® was granted an accelerated approval by the FDA as monotherapy for the treatment of MM in adult patients who have received at least four prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and an anti-CD38 mAb, and who have demonstrated disease progression on the last therapy.41 Belantamab mafodotin was evaluated in this indication in the open-label, multicenter Phase 2 DREAMM-2 (NCT03525678) study. Patients received IV administration of either belantamab mafodotin at 2.5 mg/kg or 3.4 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. ORR was the primary endpoint of the study. Treatment with single-agent belantamab mafodotin, administered as 2.5 mg/kg doses every 3 weeks, resulted in an ORR of 31% (97.5% CI: 21%, 43%).42 The prescribing information for Blenrep® includes a boxed warning due to alterations in vision, including severe vision loss and corneal ulcer, and the drug is available only through a restricted distribution program.