Chimeric antigen receptor T-cell therapy toxicities.

Area of Science:

• Oncology
• Immunology
• Cell Therapy

Background:

• Chimeric antigen receptor (CAR) T-cell therapy represents a significant advancement in cancer immunotherapy, utilizing genetically engineered T-cells to combat malignant diseases.
• While effective against B-cell lymphoid malignancies, CAR T-cell therapy is being investigated for broader applications.
• This innovative adoptive cell therapy introduces a unique set of immune-mediated adverse events and toxicities requiring careful management.

Purpose of the Study:

• To review the spectrum of immune-mediated adverse events associated with CAR T-cell therapy.
• To discuss the clinical manifestations, grading, and management strategies for these toxicities.
• To provide insights into other CAR T-cell-related immune phenomena.

Main Methods:

• Literature review of existing studies and clinical data on CAR T-cell therapy adverse events.
• Analysis of reported cases of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.
• Synthesis of information on clinical presentation, diagnostic criteria, and therapeutic interventions.

Main Results:

• CAR T-cell engagement with tumor cells triggers cytokine release, potentially leading to cytokine release syndrome (CRS).
• CRS can manifest as fever, hypotension, and hypoxia, necessitating immune-modulatory treatment.
• Immune effector cell-associated neurotoxicity syndrome (ICANS) involves blood-brain barrier disruption, cognitive decline, and potentially seizures or cerebral edema.

Conclusions:

• Effective management of CRS and ICANS is crucial for patient safety in CAR T-cell therapy.
• Understanding the mechanisms and clinical features of these toxicities aids in timely diagnosis and intervention.
• Further research and standardized protocols are essential for optimizing CAR T-cell therapy outcomes.