TY - JOUR
T1 - T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA
AU - van de Donk, Niels W. C. J.
AU - O’Neill, Chloe
AU - de Ruijter, Maaike E. M.
AU - Verkleij, Christie P. M.
AU - Zweegman, Sonja
N1 - Publisher Copyright: Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - Purpose of review B-cell maturation antigen (BCMA)-directed T-cell immunotherapies, such as chimeric antigen receptor T-cells (CAR T-cells) and bispecific antibodies (BsAbs) have markedly improved the survival of triple-class refractory multiple myeloma (MM). However, the majority of patients still develops disease progression, underlining the need for new agents for these patients. Recent findings Novel T-cell redirecting BsAbs targeting alternative tumor-associated antigens have shown great promise in heavily pretreated MM, including patients previously exposed to BCMA-directed therapies. This includes the G-protein-coupled receptor class 5 member D (GPRC5D)-targeting BsAbs talquetamab and forimtamig, as well as the Fc receptor-homolog 5 (FcRH5)-targeting BsAb cevostamab. Toxicity associated with these BsAbs includes cytokine-release syndrome, cytopenias, and infections. In addition, GPRC5D-targeting BsAbs are associated with specific ‘on target/off tumor’ toxicities including rash, nail disorders, and dysgeusia. Trispecifc antibodies targeting two different MM-associated antigens to prevent antigen escape are in early clinical development, as well as trispecific antibodies (TsAbs) that provide an additional co-stimulatory signal to T-cells to prevent their exhaustion. Summary Various T-cell redirecting BsAbs are in advanced stages of clinical development with promising activity and a manageable toxicity profile. Ongoing studies are evaluating combination strategies, fixed-duration treatment, and use of BsAbs in earlier lines of therapy. TsAbs hold great promise for the future.
AB - Purpose of review B-cell maturation antigen (BCMA)-directed T-cell immunotherapies, such as chimeric antigen receptor T-cells (CAR T-cells) and bispecific antibodies (BsAbs) have markedly improved the survival of triple-class refractory multiple myeloma (MM). However, the majority of patients still develops disease progression, underlining the need for new agents for these patients. Recent findings Novel T-cell redirecting BsAbs targeting alternative tumor-associated antigens have shown great promise in heavily pretreated MM, including patients previously exposed to BCMA-directed therapies. This includes the G-protein-coupled receptor class 5 member D (GPRC5D)-targeting BsAbs talquetamab and forimtamig, as well as the Fc receptor-homolog 5 (FcRH5)-targeting BsAb cevostamab. Toxicity associated with these BsAbs includes cytokine-release syndrome, cytopenias, and infections. In addition, GPRC5D-targeting BsAbs are associated with specific ‘on target/off tumor’ toxicities including rash, nail disorders, and dysgeusia. Trispecifc antibodies targeting two different MM-associated antigens to prevent antigen escape are in early clinical development, as well as trispecific antibodies (TsAbs) that provide an additional co-stimulatory signal to T-cells to prevent their exhaustion. Summary Various T-cell redirecting BsAbs are in advanced stages of clinical development with promising activity and a manageable toxicity profile. Ongoing studies are evaluating combination strategies, fixed-duration treatment, and use of BsAbs in earlier lines of therapy. TsAbs hold great promise for the future.
KW - Fc receptor-homolog 5
KW - G-protein-coupled receptor class 5 member D
KW - bispecific antibody
KW - multiple myeloma
KW - trispecific antibody
UR - http://www.scopus.com/inward/record.url?scp=85174841978&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/CCO.0000000000000983
DO - https://doi.org/10.1097/CCO.0000000000000983
M3 - Review article
C2 - 37501530
SN - 1040-8746
VL - 35
SP - 601
EP - 611
JO - Current opinion in oncology
JF - Current opinion in oncology
IS - 6
ER -