Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma

Abstract

BackgroundPatients with relapsed or refractory (R/R) lymphomas have benefited from chimeric antigen receptor (CAR)-T-cell therapy. However, this treatment is linked to a high frequency of adverse events (AEs), such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematologic toxicity. There has been increasing interest in hematological toxicity in recent years, as it can result in additional complications, such as infection or hemorrhage, which remain intractable.MethodsWe conducted a retrospective, single-institution study to evaluate the patterns and outcomes of cytopenia following CAR-T-cell infusion and potential associated factors.ResultsOverall, 133 patients with R/R lymphoma who received CAR-T-cell therapy from June, 2017 to April, 2022 were included in this analysis. Severe neutropenia, anemia and thrombocytopenia occurred frequently (71, 30 and 41%, respectively) after CAR-T-cell infusion. A total of 98% of severe neutropenia and all severe thrombocytopenia cases occurred in the early phase. Early severe cytopenia was associated with CRS incidence and severity, as well as peak inflammatory factor (IL-6, C-reactive protein (CRP), and ferritin) levels. In multivariate analysis, prior hematopoietic stem cell transplantation (HSCT), baseline hemoglobin (HB), and lymphodepleting chemotherapy were independent adverse factors associated with early severe cytopenia. In addition, 18% and 35% of patients had late neutrophil- and platelet (PLT)-related toxicity, respectively. In multivariate analysis, lower baseline PLT count was an independent factor associated with late thrombocytopenia. More severe cytopenia was associated with higher infection rates and poorer survival.ConclusionsThis research indicates that improved selection of patients and management of CRS may help to decrease the severity of cytopenias and associated AEs and improve survival following CAR-T-cell therapy.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03196830, identifier NCT03196830.

Hematopoiesis and immune reconstitution after CD19 directed chimeric antigen receptor T‐cells (CAR‐T): A comprehensive review on incidence, risk factors and current management

“…CD8+ T‐cells and CD56+ natural killer (NK) cells fully recovered in all patients by 1 year, while reconstitution of CD4+ T cells was delayed, with normalization in only 67% of patients at 1 year. Similarly, in 39 CAR‐T recipients with R/R, the absolute counts of CD4+, CD8+, and CD16/56+ lymphocytes decreased significantly after lymphodepleting chemotherapy: while CD8+ and CD16/CD56+ cell counts rapidly recovered in all patients at a median time of 21 days, 7–10,12–15,17,21,22,24–64,66–92 a slower recovery was observed for CD4+, which recovered within 60 days in only 5 (23.81%) of patients 71 …”

“…In a recent retrospective study of 133 patients, lomustine/etoposide/cytarabinebased lymphodepletion, and prior HSCT were independently associated with early thrombocytopenia, but not with late hematologic toxicity. 15 Prior bone marrow infiltration and the number of prior lines of chemotherapy and/or radiotherapy may also contribute to bone marrow dysfunction and lead to persistent cytopenias after CAR-T therapy. 8,10,12,15,25…”

“…Infections, including bacterial, fungal, and viral reactivations, can be both the cause and the consequence of cytopenias after CAR T-cell therapy. 15,36 However, it is still debated whether prolonged neutropenia after CAR T-cell therapy is an independent risk factor for fungal and bacterial infections. 10,15,37 Myelotoxicity due to viral infections or drugs needs to be considered when assessing cytopenic patients after CAR-T. Autoimmune cytopenias and thrombotic microangiopathy may also occur after CAR T-cell therapy, resulting in at least transient cytopenias.…”

Toxicity Profile of Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapies in Multiple Myeloma: Pathogenesis, Prevention and Management

“…However, the role of lymphodepleting therapy needs to be further studied in this context [110]. Reasonable application of corticosteroids and toci for CRS is also important, as persistent CRS appears to be a common risk factor for severe early cytopenia [111].…”

Serious adverse events and coping strategies of CAR-T cells in the treatment of malignant tumors

“…In addition, J. Zhou et al. ( 37 ) retrospectively analyzed 133 patients with R/R lymphoma who received CAR-T cells therapy. Studies have found that severe neutropenia, anemia, and thrombocytopenia frequently occur after CAR-T cells infusion.…”