TY - JOUR
T1 - T-cell redirecting bispecific antibodies targeting BCMA for the treatment of multiple myeloma
AU - Verkleij, Christie P.M.
AU - Frerichs, Kristine A.
AU - Broekmans, Marloes
AU - Absalah, Saida
AU - Maas-Bosman, Patricia W.C.
AU - Kruyswijk, Sandy
AU - Nijhof, Inger S.
AU - Mutis, Tuna
AU - Zweegman, Sonja
AU - van de Donk, Niels W.C.J.
PY - 2020/11/10
Y1 - 2020/11/10
N2 - 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.
AB - 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.
KW - BCMA
KW - Bispecific antibody
KW - CD38
KW - Immunotherapy
KW - Multiple myeloma
UR - http://www.scopus.com/inward/record.url?scp=85096110041&partnerID=8YFLogxK
U2 - https://doi.org/10.18632/oncotarget.27792
DO - https://doi.org/10.18632/oncotarget.27792
M3 - Review article
C2 - 33227097
SN - 1949-2553
VL - 11
SP - 4076
EP - 4081
JO - Oncotarget
JF - Oncotarget
IS - 45
ER -