Immune effector cell-associated haematotoxicity after CAR T-cell therapy: From mechanism to management Review
| Authors: | Rejeski, K.; Jain, M. D.; Shah, N. N.; Perales, M. A.; Subklewe, M. |
| Review Title: | Immune effector cell-associated haematotoxicity after CAR T-cell therapy: From mechanism to management |
| 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. © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license |
| Keywords: | mortality; review; pathophysiology; flow cytometry; diagnostic accuracy; t lymphocyte; tumor associated leukocyte; t-lymphocytes; cancer immunotherapy; neutrophil count; gene expression; blood toxicity; morbidity; prevalence; gene frequency; hematopoietic stem cell transplantation; cell differentiation; cytotoxicity; risk factor; immunology; immune response; neutrophil; systematic review; antigen recognition; chimeric antigen receptor; cell therapy; mesenchymal stem cell; effector cell; upregulation; hematopoietic stem cell; virus load; cytokine release; immunosuppressive treatment; granulocyte colony stimulating factor; granulocyte colony-stimulating factor; therapy; adoptive immunotherapy; immunotherapy, adoptive; immunocompetent cell; predictive value; hematologic disease; platelet count; antibody dependent cellular cytotoxicity; hematologic diseases; erythrophagocytosis; ferritin blood level; etiology; adverse event; procedures; three-dimensional imaging; humans; human; infusion therapy; chimeric antigen receptor natural killer cell immunotherapy; receptors, chimeric antigen |
| Journal Title: | The Lancet Haematology |
| Volume: | 11 |
| Issue: | 6 |
| ISSN: | 2352-3026 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2024-06-01 |
| Start Page: | e459 |
| End Page: | e470 |
| Language: | English |
| DOI: | 10.1016/s2352-3026(24)00077-2 |
| PUBMED: | 38734026 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- Erratum added, see DOI: 10.1016/S2352-3026(24)00179-0 -- Source: Scopus |
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