T-cell redirecting bispecific antibodies targeting BCMA for the treatment of multiple myeloma
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Christie P.M. Verkleij1,*, Kristine A. Frerichs1,*, Marloes Broekmans1, Saida Absalah1, Patricia W.C. Maas-Bosman1, Sandy Kruyswijk1, Inger S. Nijhof1, Tuna Mutis1, Sonja Zweegman1 and Niels W.C.J. van de Donk1
1 Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands
* Shared first authors
|Niels W.C.J. van de Donk,||email:||[email protected]|
Keywords: multiple myeloma; bispecific antibody; immunotherapy; BCMA; CD38
Received: October 09, 2020 Accepted: October 13, 2020 Published: November 10, 2020
B-cell maturation antigen (BCMA)-targeting bispecific antibodies and bispecific T-cell engagers (BiTEs) redirect T-cells to BCMA-expressing multiple myeloma (MM) cells. These MM cells are subsequently eliminated via various mechanisms of action including the release of granzymes and perforins. Several phase 1, dose-escalation studies show pronounced activity of BCMA-targeting bispecific antibodies, including teclistamab, AMG420 and CC-93269, in heavily pretreated MM patients. Cytokine release syndrome is the most common adverse event, which can be adequately managed with tocilizumab or steroids. Several clinical trials are currently evaluating combination therapy with a BCMA-specific bispecific antibody, based on preclinical findings showing that immunomodulatory drugs or CD38-targeting antibodies enhance the activity of bispecific antibodies. In addition, bispecific antibodies, targeting other MM cell surface antigens (i. e. GPRC5D, CD38 and FcRH5), are also evaluated in early phase clinical trials. Such bispecific antibodies, targeting other antigens, may be given to patients with low baseline BCMA expression, disease with substantial heterogeneity in BCMA expression, following prior BCMA-targeted therapy, or combined with BCMA bispecific antibodies to prevent development of antigen escape.
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