daratumumab + imlifidase

Daratumumab + imlifidase is an investigational combination therapy consisting of two biologic agents. Daratumumab is a human IgG1k monoclonal antibody that targets CD38, a cell surface protein highly expressed on multiple myeloma cells. It induces tumor cell death through mechanisms such as complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis, as well as by depleting immunosuppressive regulatory cells expressing CD38[6][8]. Imlifidase is a recombinant cysteine protease enzyme that cleaves human IgG antibodies at the hinge region, rapidly reducing circulating IgG levels. The rationale for combining these agents is to enable or enhance daratumumab therapy in patients with anti-drug antibodies (ADAs) or other pre-existing anti-IgG responses that may limit efficacy. This combination has been explored primarily in the context of multiple myeloma and related plasma cell disorders.