An International Survey on Grading, Diagnosis, and Management of Immune Effector Cell-Associated Hematotoxicity (ICAHT) Following CAR T-cell Therapy on Behalf of the EBMT and EHA.

Hematological toxicity represents the most common grade ≥3 toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, its underlying pathophysiology is incompletely understood and its grading and management remains ill-defined. To inform the forthcoming European Hematology Association/European Society for Blood and Marrow Transplantation (EHA/EBMT) guidelines on the management of "immune effector cell-associated hematotoxicity" (ICAHT), we undertook a survey of experienced clinicians using an online survey focusing on (1) grading, (2) risk-stratification and diagnostic work-up, (3) short-term, and (4) long-term management of ICAHT. There were 81 survey respondents across 18 countries. A high degree of variability was noted for cytopenia grading in regards to depth, duration, and time from CAR-T infusion. The majority of experts favored pre-CAR-T bone marrow studies, especially in case of a high-risk profile. Most respondents felt that the work-up for patients with severe hematotoxicity should rule-out viral infections (96%), substrate deficiency (80%), or coincident sHLH/MAS (serum ferritin, 92%), and should include bone marrow aspiration (86%) and/or biopsy (61%). Clinicians were divided as to whether the occurrence of coincident immunotoxicity should influence the decision to apply G-CSF, and when to initiate G-CSF support. In case of prolonged thrombocytopenia, most survey participants favored thrombopoietin agonists (86%). Conversely, autologous hematopoietic cell boosts represented the preferred choice for neutropenia (63%), although they were frequently not available and no consensus was reached regarding the optimal trigger point. These findings underline the current heterogeneity of practice patterns regarding ICAHT and invite the development of consensus guidelines, which may harmonize grading, establish standard operating procedures for diagnosis, and set management guidelines.

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Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.

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KR: Kite/Gilead: Research Funding and travel support; Novartis: Honoraria; BMS/Celgene: Consultancy, Honoraria; School of Oncology of the German Cancer Consortium (DKTK): fellowship; Else Kröner Forschungskolleg (EKFK) within the Munich Clinician Scientist Program (MCSP): funding. FO: Travel, Accommodations, Expenses: Takeda, Kyowa Kirin International, Medac. CB: inventor of different patents on cancer immunotherapy and genetic engineering; member of Advisory Boards and Consultant for, Intellia, Kite/Gilead, Miltenyi, Kiadis, QuellTx, Janssen, Chroma, Genyo, Pancancer-T, Alia, and received research support from Intellia Therapeutics. AS: Honoraria: Takeda, Bristol Myers Squibb, Merck Sharp and Dohme, Celgene, Janssen, Sanofi, Roche, Novartis, Gilead Sciences, Janssen-Cilag; Consulting or Advisory Role: Takeda, Bristol Myers Squibb, Gilead Sciences, Celgene, Janssen, Novartis; Speakers’ Bureau: Takeda; Travel, Accommodations, Expenses: Kite/Gilead. JGG: Received honoraria from Amgen, BMS Gilead/Kite, Janssen, Novartis, and received research funding from AZ, BMS and Janssen. IY-A: Received honoraria from Novartis, Gilead/Kite, BMS and Janssen. MS: Morphosys: Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Seattle Genetics: Research Funding; AMGEN: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Research Funding; Roche AG: Consultancy, Research Funding. None of the mentioned conflicts of interest were related to financing of the content of this article. All the other authors have no conflicts of interest to disclose.