Daratumumab (trade name: Darzalex) is a revolutionary breakthrough in the treatment of multiple myeloma. It is a humanized anti-CD38 monoclonal antibody discovered and developed by the Danish biotechnology company Genmab, and subsequently licensed to Janssen Biotech for global commercialization in 2012. The drug has a unique mechanism of action, directly killing tumor cells by binding with high affinity to the CD38 glycoprotein highly expressed on the surface of multiple myeloma cells, activating multiple immune mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and phagocytosis (ADCP), while also possessing immunomodulatory effects. Based on its significant efficacy in monotherapy for patients with relapsed and refractory multiple myeloma, daratumumab received accelerated approval from the US FDA on November 16, 2015, becoming the first approved CD38-targeted drug. Subsequently, its indications expanded rapidly, especially based on pivotal phase III clinical trials such as the CASTOR (daratumumab in combination with bortezomib and dexamethasone) and POLLUX (daratumumab in combination with lenalidomide and dexamethasone) trials. These trials demonstrated that daratumumab in combination with standard therapy could significantly improve patients' progression-free survival, thus making it a cornerstone of first- and second-line treatment options for multiple myeloma.
Daratumumab (Anti-Human CD38) is the first-in-class human-specific anti-CD38 monoclonal antibody (IgG1). Daratumumab has anti-multiple myeloma (MM) effect. Daratumumab impairs MM cell adhesion, which results in an increased sensitivity of MM to proteasome inhibition[1][2].
