Published on February 14, 2025
Graft-Versus-Host Disease After CAR T-Cell Therapy in AlloHCT Patients: A Multi-Center Perspective
by Alex Kadhim
Recent studies from Vall d’Hebron University Hospital, Heidelberg University Hospital, and the European Society for Blood and Marrow Transplantation (EBMT) provide valuable insights into the incidence and management of graft-versus-host disease (GvHD) following anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients who previously underwent allogeneic hematopoietic cell transplantation (alloHCT). Given that CAR T-cells derived post-alloHCT may originate from donor T-cells, concerns about their potential allo-reactivity and GvHD risk remain a critical safety consideration. Data from an EBMT registry-based study analyzing 257 alloHCT patients (172 adults) treated with CD19-directed CAR T-cells between 2018 and 2022 found that acute GvHD (aGvHD) occurred in only 1.6% of cases within 100 days, while chronic GvHD (cGvHD) was observed in 2.8% of patients within 12 months. With a median follow-up of 18.8 months, the one-year overall survival (OS) was 76.8%, and non-relapse mortality remained low at 4.7%. These findings suggest that CAR T-cell therapy does not significantly increase the risk of GvHD in this population.
A separate retrospective study from Heidelberg University Hospital examined 25 alloHCT recipients who received CD19-directed CAR T-cell therapy. Of these, 11 patients exhibited symptoms suggestive of GvHD, with 3 (12%) developing confirmed GvHD likely triggered by CAR T-cell therapy. Notably, one patient developed severe chronic pulmonary GvHD. The study also highlighted the successful use of extracorporeal photopheresis (ECP) in controlling GvHD without causing relapse of the underlying malignancy. These results indicate that while GvHD occurrence post-CAR T-cell therapy remains relatively low, it may be underestimated, necessitating further investigation into risk factors, including donor compatibility, T-cell source, and CAR construct variations.
Despite the potential risks, both studies emphasize the feasibility of CD19-directed CAR T-cell therapy in alloHCT patients, demonstrating high survival rates and effective GvHD management strategies. The overall low GvHD incidence supports the use of CAR T-cell therapy in this setting, though careful patient selection and early intervention strategies, such as ECP, may help mitigate complications. Future research should explore predictive biomarkers for GvHD development and optimize post-CAR T-cell monitoring protocols to enhance patient safety and long-term outcomes.
References
Ortí G, Peczynski C, Boreland W, et al. Graft-versus-host disease after anti-CD19 chimeric antigen receptor T-cell therapy following allogeneic hematopoietic cell transplantation: a transplant complications and paediatric diseases working parties joint EBMT study. Leukemia. Published online November 19, 2024.
http://doi.org/10.1038/s41375-024-02467-5
Farid KMN, Bug G, Schmitt A, et al. GVHD after CAR T-cell therapy post allogeneic hematopoietic cell transplantation - successfully treated by extracorporeal photopheresis. Front Immunol. 2024;15:1500177. Published 2024 Nov 18.
http://doi.org10.3389/fimmu.2024.1500177
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