Researchers have begun the search for genetic changes that might predispose patients undergoing CAR-T cell therapy to the risk of developing T cell lymphoma.
German scientists conducted a detailed study of a patient treated for multiple myeloma with CAR-T therapy. The patient developed T cell lymphoma in the blood, skin and intestines nine months after the treatment. Nine other cases of this complication have been reported worldwide.
The researchers used next generation sequencing, whole genome sequencing and single cell RNA sequencing. They say they succeeded in undertaking their research in “a very short time” thanks to the close collaboration between clinicians and lab scientists.
Reporting in Nature Medicine, the researchers at the University of Leipzig Medical Centre, report that the patient’s tumour developed from the CAR-T cells used in the treatment. However, pre-existing changes in the patient’s haematopoietic cells played a role, as well as genetic alterations linked to integration of the gene for the chimeric antigen receptor (CAR).
They hope the research will open the way to identifying patients at risk of complications from CAR-T treatment.
Study leader Professor Maximilian Merz said: “This is one of the first documented cases of such lymphoma following CAR-T cell therapy. The findings of this study will help us to better understand the risks associated with the therapy and possibly prevent them in the future.
“This case provides valuable insights into the emergence and development of CAR-bearing T cell lymphoma following innovative immunotherapies and highlights the importance of genetic predispositions for potential side effects.”
Source:
Braun T, Rade M, Merz M, Klepzig H, Große F, Fandrei D, Pham NN, Kreuz M, Kuhn CK, Kuschel F, Löffler D, Meinel J, Heger E, Schweinsberg V, Pflug N, Platzbecker U, Hallek M, Holtick U, Köhl U, Scheid C, Reiche K, Herling M, Richardson T. (2025) “Multiomic profiling of T cell lymphoma after therapy with anti-BCMA CAR T cells and GPRC5D-directed bispecific antibody.” Nature Medicine, 21 February 2025, doi: 10.1038/s41591-025-03499-9.
Link: https://www.nature.com/articles/s41591-025-03499-9
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