TY - JOUR
T1 - BCMA-directed therapy, new treatments in the myeloma toolbox, and how to use them
AU - Rees, Matthew James
AU - Kumar, Shaji
N1 - Publisher Copyright:
© 2023 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2024
Y1 - 2024
N2 - To address the dearth of therapeutic options available for relapsed-refractory multiple myeloma (RRMM), attention has shifted to immunotherapeutic strategies, with most products in development targeting the B-cell maturation antigen (BCMA). BCMA is a transmembrane receptor of the tumor necrosis factor receptor superfamily, essential for plasma cell survival and minimally expressed on non-hematopoietic tissues; it represents an ideal therapeutic target. Three categories of BCMA-directed therapies exist, with distinct strengths and weaknesses. Antibody–drug conjugates (ADCs) are immediately available with modest single-agent efficacy in RRMM, but deliverability is hampered by corneal toxicity. CAR T-cells are the most effective class but face significant logistical and financial barriers. Bispecific antibodies offer superior efficacy and tolerability compared to ADCs, but prolonged exposure causes significant cumulative infectious risk. In this review, we will examine the role of BCMA in MM biology, the approved and emerging therapies targeting this antigen, and how these agents can be optimally sequenced.
AB - To address the dearth of therapeutic options available for relapsed-refractory multiple myeloma (RRMM), attention has shifted to immunotherapeutic strategies, with most products in development targeting the B-cell maturation antigen (BCMA). BCMA is a transmembrane receptor of the tumor necrosis factor receptor superfamily, essential for plasma cell survival and minimally expressed on non-hematopoietic tissues; it represents an ideal therapeutic target. Three categories of BCMA-directed therapies exist, with distinct strengths and weaknesses. Antibody–drug conjugates (ADCs) are immediately available with modest single-agent efficacy in RRMM, but deliverability is hampered by corneal toxicity. CAR T-cells are the most effective class but face significant logistical and financial barriers. Bispecific antibodies offer superior efficacy and tolerability compared to ADCs, but prolonged exposure causes significant cumulative infectious risk. In this review, we will examine the role of BCMA in MM biology, the approved and emerging therapies targeting this antigen, and how these agents can be optimally sequenced.
KW - B-cell maturation antigen
KW - T-cell engager
KW - antibody drug conjugates
KW - bispecific antibodies
KW - chimeric antigen receptor T-cells
KW - multiple myeloma
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U2 - 10.1080/10428194.2023.2284088
DO - 10.1080/10428194.2023.2284088
M3 - Review article
C2 - 38354090
AN - SCOPUS:85177446203
SN - 1042-8194
VL - 65
SP - 287
EP - 300
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 3
ER -