Kiavasch M. Farid ¹ Gesine Bug ² Anita Schmitt ¹ Fabian Lang ² Maria-Luisa Schubert ¹ Uwe Haberkorn ³ Carsten Müller-Tidow ¹ Peter Dreger ¹ Michael Schmitt ^1*

• ¹ Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany
• ² Goethe University Frankfurt, University Hospital, Department of Medicine 2, Hematology and Oncology, Frankfurt am Main, Germany
• ³ Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Baden-Württemberg, Germany

CAR T-cell therapy is highly effective, but also associated with unique toxicities. Due to the origin of T-cells in patients who previously underwent allogeneic hematopoietic cell transplantation (alloHCT), graft-versus-host disease (GVHD) in the post-CAR T-cell setting poses a relevant concern but is only scarcely studied. Potential risk factors and mitigation strategies (from CAR T-cell modifications to clinical management) are yet to be determined. Sharing our own experience and a mini-review of the literature, our aim is to better understand frequency and risk of the potential occurrence of GVHD after CAR T-cells, which are most likely underestimated. Here, we present a cohort of 11 patients with symptoms suggestive of GVHD out of 25 allografted patients treated with CAR T-cells, of whom 3 patients (12%) had GVHD most likely triggered by the preceding CAR T-cell treatment. Severe chronic pulmonary GVHD occurred in a patient after CD19-directed CAR T-cell therapy. Extracorporeal photopheresis (ECP) mediated successful resolution long-term control of GVvHD without causing relapse of the underlying disease. In conclusion, CD19-directed CAR T-cell therapy seems to be feasible in patients after alloHCT but might comprise the potential risk of triggering GVHD, most likely depending on the T-cell source, donor compatibility and the specific CAR construct used.