CD22 CAR T-cell associated hematologic toxicities, endothelial activation and relationship to neurotoxicity

作者：Jennifer Jess, Bonnie C. Yates, Alina Dulau‐Florea, Kevin R. Parker, Jon R. Inglefield, Daniel A. Lichtenstein, Fiorella Schischlik, Martin Ongkeko, Yanyu Wang, Shilpa A. Shahani, Ann Cullinane, Hannah E Smith, Eli Kane, Lauren M Little, Dong Chen, Terry J. Fry, Haneen Shalabi, Hao‐Wei Wang, Ansuman T. Satpathy, Jay Nelson Lozier, Nirali N. Shah · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2023 · DOI：10.1136/jitc-2022-005898 · 被引用次数：35 · 研究领域：CAR-T cell therapy research、Cutaneous lymphoproliferative disorders research、Lymphoma Diagnosis and Treatment

BACKGROUND: Hematologic toxicities, including coagulopathy, endothelial activation, and cytopenias, with CD19-targeted chimeric antigen receptor (CAR) T-cell therapies correlate with cytokine release syndrome (CRS) and neurotoxicity severity, but little is known about the extended toxicity profiles of CAR T-cells targeting alternative antigens. This report characterizes hematologic toxicities seen following CD22 CAR T-cells and their relationship to CRS and neurotoxicity. METHODS: We retrospectively characterized hematologic toxicities associated with CRS seen on a phase 1 study of anti-CD22 CAR T-cells for children and young adults with relapsed/refractory CD22+ hematologic malignancies. Additional analyses included correlation of hematologic toxicities with neurotoxicity and exploring effects of hemophagocytic lymphohistiocytosis-like toxicities (HLH) on bone marrow recovery and cytopenias. Coagulopathy was defined as evidence of bleeding or abnormal coagulation parameters. Hematologic toxicities were graded by Common Terminology Criteria for Adverse Events V.4.0. RESULTS: Across 53 patients receiving CD22 CAR T-cells who experienced CRS, 43 (81.1%) patients achieved complete remission. Eighteen (34.0%) patients experienced coagulopathy, of whom 16 had clinical manifestations of mild bleeding (typically mucosal bleeding) which generally subsided following CRS resolution. Three had manifestations of thrombotic microangiopathy. Patients with coagulopathy had higher peak ferri...