Cytopenia after CAR-T Cell Therapy—A Brief Review of a Complex Problem

SIMPLE SUMMARY: Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has emerged as a new life-saving treatment modality in patients with relapsed or refractory B-cell malignancies and multiple-myeloma. In this form of therapy, patient’s T-cells are modified by various genetic techniques to express a new receptor that identifies and kills the cancer cells. With increasing use, they present with distinct immune mediated side effects such as cytokine release syndrome (CRS), neurotoxicity, and prolonged cytopenia. While our understanding of CRS and other immune side-effects has increased, prolonged cytopenia post CAR-T infusion remains under-recognized and under-reported. With the focus on prolonged cytopenia in this review, we aim to summarize findings of various clinical trials, postulated mechanisms, and clinical interventions to risk-stratify and manage this clinical entity. ABSTRACT: Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has emerged as an efficacious and life extending treatment modality with high response rates and durable remissions in patients with relapsed and refractory non-Hodgkin lymphoma (NHL), follicular lymphoma, and B-cell acute lymphoblastic leukemia (B-ALL) as well as in other diseases. Prolonged or recurrent cytopenias after CAR-T therapy have increasingly been reported at varying rates, and the pathogenesis of this complication is not yet well-understood but is likely contributed to by multiple factors. Current studies reported are primarily retrospective, heterogeneous in terms of CAR-Ts used and diseases treated, non-uniform in definitions of cytopenias and durations for end points, and vary in terms of recommended management. Prospective studies and correlative laboratory studies investigating the pathophysiology of prolonged cytopenias will enhance our understanding of this phenomenon. This review summarizes knowledge of these cytopenias to date.