Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations

Area of Science:

• Hematology
• Immunotherapy
• Oncology

Background:

• Hematological toxicity, including cytopenias, is the most frequent adverse event following chimeric antigen receptor (CAR) T-cell therapy, leading to significant infectious risks.
• Existing practices for managing CAR T-cell therapy-related hematotoxicity show considerable heterogeneity worldwide.
• There is a need for standardized guidelines to address the grading and management of immune effector cell-associated hematotoxicity (ICAHT).

Approach:

• An international panel of 36 CAR T-cell experts from the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA) convened to develop consensus recommendations.
• Deliberations involved virtual conferences and a 2-day meeting to establish best practices for ICAHT.
• Recommendations cover grading, risk factors, diagnostic workup, and management strategies for ICAHT.

Key Points:

• A novel classification system for grading ICAHT is proposed, based on the depth and duration of neutropenia for early (day 0-30) and late (after day +30) phases.
• Guidance is provided on identifying hemophagocytosis in severe hematotoxicity cases.
• Consensus recommendations address management including growth factor support, anti-infective prophylaxis, transfusions, and stem cell interventions.

Conclusions:

• Immune effector cell-associated hematotoxicity (ICAHT) is proposed as a distinct toxicity category following immune effector cell therapy.
• A framework for grading ICAHT, including risk factor assessment and diagnostic workup, is established.
• Expert recommendations offer a comprehensive approach to the short- and long-term management of ICAHT, aiming to standardize care and improve patient safety.