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Commentary Open Access

Non-canonical CAR-T cell-related toxicities: Emerging strategies and challenges

  • 1Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy
  • 2Department of Biomedicina e Prevenzione, Tor Vergata University, 00133 Rome, Italy
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Corresponding Author

Martina Canichella, martina.canichella@aslroma2.it

Received Date: August 28, 2025

Accepted Date: October 01, 2025

Abstract

CAR-T cell therapy revolutionized the treatment of patients with relapsed or refractory B-cell hematologic malignancies, substantially altering their prognosis. Alongside its remarkable efficacy, however, this approach is frequently accompanied by treatment-related toxicities. While cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are the best characterized and usually manageable with standard interventions, a spectrum of additional, non-canonical complications has gained increasing clinical recognition. These include persistent cytopenias (immune effector cell–associated hematologic toxicity, ICAHT), immune effector cell–associated hemophagocytic lymphohistiocytosis–like syndrome (IEC-HS), and coagulopathies. Such events may manifest late, persist for prolonged periods, and significantly compromise patients’ quality of life. In this manuscript, we summarize current evidence and guideline-based recommendations regarding these non-canonical complications, with the aim of providing clinicians a practical framework for their recognition, management, and integration into routine post-infusion care.

Keywords

Chimeric antigen receptor T-cell, Cytokine release syndrome, Immune effector cell-associated neurotoxicity, Non-canonical toxicity, Immune effector cell -associated hematologic toxicity, Immune effector cell -associated hemophagocytic lymphohistiocytosis- like syndrome, Coagulopathy

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