Cytopenias and infections following ciltacabtagene autoleucel in heavily pretreated relapsed or refractory multiple myeloma

Abstract

Ciltacabtagene autoleucel (cilta-cel) was approved by the Food and Drug Administration in February 2022 for the treatment of relapsed/refractory multiple myeloma after four lines of therapy. On the CARTITUDE-1 trial, grade >3 cytopenias and infections were common. Herein, we sought to characterize cytopenias and infections after cilta-cel infusion in the standard-of-care setting. This multicenter, retrospective study included 105 patients who received cilta-cel; 91 reached day 90 and 49 reached day 180 of follow-up. Grade >3 cytopenia was present among 52% of patients on day 30, and 24% of patients on day 90. Based on the newer immune effector cell-associated hematotoxicity (ICAHT) grading for neutropenia severity, 11 patients (10%) experienced grade >3 early ICAHT in the first 30 days, while only three (3.3%) experienced grade >3 late ICAHT after day 30. On univariate analysis, any grade thrombocytopenia at apheresis was associated with grade >3 cytopenia at both days 30 and 90. Granulocyte colony-stimulating factor was administered to 65%, transfusion support to 38%, throm-bopoietin agonists to 10%, intravenous immunoglobulins to 52%, and CD34+ stem cell boosts to 9.5% of patients. Infections occurred in 49% of patients and were severe in 32%. Earlier infections in the first 30 days were equally bacterial (42%) and viral (42%). Later infections between days 31-100 and after day 100 were mostly viral (59% and 60%, respectively), with only 32% and 12% being grade >3 in each time period. On univariate analysis, worse Eastern Cooperative Oncology Group performance status at lymphodepletion, higher maximum grade of cytokine-release syndrome, delayed neurotoxicity, steroid and anakinra use, and lower IgA levels at day 90 were associated with severe infections.