Anti-CD38 monoclonal antibodies in multiple myeloma: another cook in the kitchen?

Monoclonal antibodies are a cornerstone in the treatment of multiple myeloma. Among the available anti-CD38 monoclonal antibodies, daratumumab has been approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), while isatuximab, MOR202, and TAK-079 are currently under investigation. Anti-CD38 monoclonal antibodies have several mechanisms of action, including antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, complement-dependent cytotoxicity, direct cellular apoptosis, and extracellular ectoenzyme activity modulation. 1 Bonello F D'Agostino M Moscvin M Cerrato C Boccadoro M Gay F CD38 as an immunotherapeutic target in multiple myeloma. Expert Opin Biol Ther. 2018; 18: 1209-1221 Crossref PubMed Scopus (24) Google Scholar Typical side effects of anti-CD38 monoclonal antibodies are the infusion-related reactions, which might be associated with the complement-dependent cytotoxicity activity of the compound. Infusion-related reactions mainly occur during the first infusion and primarily manifest with a respiratory pattern. 1 Bonello F D'Agostino M Moscvin M Cerrato C Boccadoro M Gay F CD38 as an immunotherapeutic target in multiple myeloma. Expert Opin Biol Ther. 2018; 18: 1209-1221 Crossref PubMed Scopus (24) Google Scholar In some patients, such as those with pre-existing chronic obstructive pulmonary disease or severe chronic asthma, infusion-related reactions can be a matter of concern, sometimes preventing patients from receiving anti-CD38 monoclonal antibodies. MOR202, a novel anti-CD38 monoclonal antibody, in patients with relapsed or refractory multiple myeloma: a first-in-human, multicentre, phase 1–2a trialMOR202 is safe and its clinical activity in patients with relapsed or refractory multiple myeloma is promising. Further clinical investigations of combinations with an immunomodulatory drug and dexamethasone are recommended. Full-Text PDF