CAR T Cell Toxicities and Emerging Treatment Strategies.

Area of Science:

• Immunotherapy
• Oncology
• Cellular Therapy

Background:

• Chimeric antigen receptor (CAR) T cell therapy has transformed treatments for B cell malignancies and multiple myeloma.
• CAR T cell therapy is expanding to target solid tumors, offering new hope for patients.

Purpose of the Study:

• To review the acute toxicities associated with CAR T cell therapy in solid tumors.
• To discuss the clinical presentation, evaluation, and management of these toxicities.
• To explore the pathophysiology and emerging mitigation strategies for CAR T cell-related adverse events.

Main Methods:

• Literature review of clinical presentations, risk factors, and pathophysiologies of CAR T cell toxicities.
• Discussion of current and emerging strategies for toxicity management.
• Synthesis of information on cytokine release syndrome, neurotoxicity, hematotoxicity, and HLH-like syndromes.

Main Results:

• Antitumor responses to CAR T cell therapy are often accompanied by immune hyperactivation.
• Key toxicities include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematotoxicity, and hemophagocytic lymphohistiocytosis-like syndrome (HLH-like).
• Understanding risk factors and pathophysiology is crucial for effective management.

Conclusions:

• CAR T cell therapy presents significant potential for solid tumors but requires careful management of associated toxicities.
• Effective strategies for evaluating, managing, and mitigating these adverse events are critical for successful clinical application.
• Ongoing research into toxicity mitigation will be vital for expanding the use of CAR T cell therapy.