daratumumab + isatuximab

Daratumumab + isatuximab is a conceptual combination of two distinct CD38-targeting monoclonal antibodies, each of which binds a different, nonoverlapping epitope on CD38 and exerts antimyeloma effects via immune-mediated and direct cytotoxic mechanisms. Daratumumab is a human IgG1κ monoclonal antibody that induces multiple myeloma cell death primarily through Fc-dependent mechanisms including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and phagocytosis, and has additional immunomodulatory effects via depletion of CD38-positive regulatory T cells, regulatory B cells, and myeloid-derived suppressor cells, thereby enhancing T‑cell number, clonality, and function.[8][6] Isatuximab is a chimeric/humanized IgG1 monoclonal antibody that binds a distinct CD38 epitope partially encompassing the ectoenzyme catalytic site and can induce direct, caspase-dependent apoptosis of myeloma cells without external cross-linking, as well as Fc-mediated ADCC, ADCP, CDC, and potent inhibition of CD38 ectoenzyme activity, contributing to reversal of adenosine-mediated immunosuppression in the myeloma microenvironment.[2][6] Although both antibodies are individually approved in combination regimens for relapsed/refractory multiple myeloma, their concurrent use together in a single therapeutic regimen is not an established or approved treatment strategy and is primarily of theoretical or experimental interest in the context of CD38 biology and resistance.

Brand names

SarclisaDarzalexDarzalex Faspro

Other names

isatuximab-irfcSAR650984SAR-650984SAR 650984