Anti-CD38 monoclonal antibodies in multiple myeloma: another cook in the kitchen?
Mené sur 91 patients atteints d'un myélome multiple réfractaire ou récidivant, cet essai de phase I-IIA évalue la dose maximale tolérée et l'immunogénicité d'un composé appelé MOR202 (un anticorps monoclonal ciblant CD38), seul, en combinaison avec la dexaméthasone ou en combinaison avec la dexaméthasone et le pomalidomide ou le lénalidomide
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. 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. 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.