CAR T cell–mediated bone marrow inflammation causes hematotoxicity and favors clonal hematopoiesis
Year: 2025
Type: article
Abstract: Although chimeric antigen receptor (CAR) T cells have shown excellent results in treating hematological malignancies, they also cause side effects. Patients treated with CAR T cells experience persistent cytopenia or hematotox. Here, using a fully immunocompetent mouse model, we recapitulated hematotox and demonstrated that a lymphodepleting regimen alone was insufficient to induce hematotox and required CAR T cell injection. Analysis of bone marrow (BM) samples from patients experiencing hematotox revealed a correlation between BM CAR T cells and hematotox severity. CAR T cells exhibited an activated program, leading to intense inflammation. In addition, we observed a high rate of clonal hematopoiesis in our patient cohort and the emergence of distinct hematopoietic clones in the months after CAR T cell injection. Our study provides insights into the pathophysiology of hematotox and highlights the need for long-term follow-up studies to determine the relevance of this intense BM inflammation in clonal selection.
Source: Science Translational Medicine
Authors: Myriam Ben Khelil, Ahmadreza Arbab, Janesa Srikanthan, Laura Marcos Kovandzic, Véronique Vergé, Arnaud Pagès, Jessica Rengassamy, Roula Amine-Hneineh, Marine Aglave, Rémy Jelin, Vincent Ribrag, Wassila Rahali, Paul-Auguste Goutebroze, Stéphane de Botton, Laurie Menger, Ileana Antony-Debré, Jean-Baptiste Micol, Christophe Marzac, Cristina Castilla Llorente, Camille Bigenwald
Institutions: Inserm, Institut Gustave Roussy, Université Paris-Saclay
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4414459434