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Rejeski, Kai ORCID logoORCID: https://orcid.org/0000-0003-3905-0251; Jain, Michael D. ORCID logoORCID: https://orcid.org/0000-0002-7789-1257; Shah, Nirali N.; Perales, Miguel-Angel und Subklewe, Marion ORCID logoORCID: https://orcid.org/0000-0001-9154-9469 (2024): Immune effector cell-associated haematotoxicity after CAR T-cell therapy: from mechanism to management. In: Lancet Haematology, Bd. 11, Nr. 6, e459-e470 [PDF, 3MB]

Abstract

Genetically engineered chimeric antigen receptor (CAR) T cells have become an effective treatment option for several advanced B-cell malignancies. Haematological side-effects, classified in 2023 as immune effector cell-associated haematotoxicity (ICAHT), are very common and can predispose for clinically relevant infections. As haematopoietic reconstitution after CAR T-cell therapy differs from chemotherapy-associated myelosuppression, a novel classification system for early and late ICAHT has been introduced. Furthermore, a risk stratification score named CAR-HEMATOTOX has been developed to identify candidates at high risk of ICAHT, thereby enabling risk-based interventional strategies. Therapeutically, growth factor support with granulocyte colony-stimulating factor (G-CSF) is the mainstay of treatment, with haematopoietic stem cell (HSC) boosts available for patients who are refractory to G-CSF (if available). Although the underlying pathophysiology remains poorly understood, translational studies from the past 3 years suggest that CAR T-cell-induced inflammation and baseline haematopoietic function are key contributors to prolonged cytopenia. In this Review, we provide an overview of the spectrum of haematological toxicities after CAR T-cell therapy and offer perspectives on future translational and clinical developments.

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