CAR-Induced Cytopenia

Abstract

AbstractCytopenias after chimeric antigen receptor (CAR) T cell therapy for hematological malignancies are common and poorly understood. The duration and degree of cytopenias vary significantly, while the reasons for delayed recovery remain unclear. In pivotal trials, over 50% patients had anemia and thrombocytopenia, while over 70% patients had neutropenia and leukopenia amongst those receiving axicabtagene ciloleucel or tisagenlecleucel for B cell lymphoma. While lymphodepletion chemotherapy was thought to be the cause of cytopenias, subsequent studies have suggested correlation with degree of inflammation. In an 83-patient study from Memorial Sloan Kettering Cancer Center in patients with relapsed/refractory B cell lymphoma or multiple myeloma, the majority patients had “recovered” (defined as hemoglobin >8 g/dL, platelets >50×103/µL, and absolute neutrophil count >1000/µL (without transfusion or growth factor support) at 3 months.1 Specifically, hemoglobin, platelet, neutrophil and white blood cell counts had “recovered” in 61%, 51%, 33%, and 28% patients, respectively, at 1 months, and 93%, 90%, 80%, and 59% patients at 3 months, respectively following CAR T cell infusion. To avoid confounding from marrow involvement with disease, only patients in remission were included in this analysis. In a univariate analysis, the following were statistically significantly associated with lower incidence of count recovery at 1 month: (1)higher grade of immune effector cell-associated neurological syndrome (ICANS),(2)pre-existing cytopenias at the time of CAR T infusion,(3)axicabtagene ciloleucel (versus tisagenlecleucel), and (4) higher peak C-reactive protein or ferritin levels.