CD38 antibodies in patients with relapsed/refractory multiple myeloma

Advances in treatment options forpatients with multiple myeloma have made a significant impact on overall survival and have helpedto achieve the rates of response and duration ofremission previously not unachievable with standard chemotherapy-based approaches. This articlereviews therapeutic efficacy and safety, dosage andadministration, peculiar properties of the practical application of CD38 antibodies. CD38 is highlyand uniformly expressed on multiple myeloma(MM) cells, and at relatively low levels on normallymphoid and myeloid cells, and in some tissues ofnonhematopoietic origin. CD38 is a transmembran eglycoprotein with ectoenzymatic activity, and alsofunctions as a receptor and adhesion molecule.Altogether, this has triggered the development ofseveral CD38 antibodies including daratumumab(fully human), isatuximab (chimeric), and MOR202(fully human). In 2008, the fully human immunoglobulin G1-k (IgG1-k) antibody daratumumab, wasthe first CD38 antibody that was administered inMM. Daratumumab was selected from a panel of42 antibodies based on its unique ability to inducecomplement dependent cytotoxicity. Daratumumabalso kills MM cells via antibody-dependent cellular cytoxicity and antibody-dependent cellularphagocytosis via antibody binding to activatingFcg receptors on immune effector cells. It shouldalso be highlighted that the recently approved mAbdaratumumab has shown efficacy as monotherapy in patients with RRMM who have received aminimum of five previous lines of therapy or whohad disease that was double refractory to IMiDsand PIs in the phase II SIRIUS and GEN501 study.Daratumumab is also indicated in combinationwith lenalidomide plus dexamethasone and withbortezomib plus dexamethasone. In the phaseIII POLLUX study, the addition of daratumumabto lenalidomide and dexamethasone significantly increased PFS (not reached vs. 17.5 months;