Recognizing, defining, and managing CAR-T hematologic toxicities.

Area of Science:

• Oncology
• Immunology
• Hematology

Background:

• Autologous CAR-T cell therapy (CAR-T) offers improved outcomes for B-cell malignancies but presents known toxicities like CRS and ICANS.
• Beyond canonical toxicities, CAR-T is associated with significant hematologic adverse events requiring careful management.

Approach:

• This review synthesizes current understanding of CAR-T-related hematologic toxicities, including cytopenias, coagulopathies, and hemophagocytic lymphohistiocytosis.
• Focus is placed on immune effector cell-associated hematological toxicity (ICAHT), its early and late presentations, and management strategies.
• Diagnostic criteria and management guidelines for ICAHT and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) are discussed.

Key Points:

• ICAHT is the most common immune-related adverse event post-CAR-T, with distinct early and late phases.
• Growth factor support, particularly early G-CSF, is a primary treatment for cytopenias.
• The CAR-HEMATOTOX scoring system aids in pretherapeutic risk assessment for CAR-T patients.

Conclusions:

• Effective management of CAR-T-associated hematologic toxicities is essential for patient safety and treatment success.
• Standardized diagnostic criteria and risk stratification tools like CAR-HEMATOTOX are vital for risk-adapted management.
• Further research and clinical vigilance are necessary to optimize care for patients undergoing CAR-T therapy.