Leukemia types, such as lymphoma and multiple myeloma, are malignant tumors, which derive from the body’s defensive cells, the lymphocytes. Over the last few years, CAR-T cell therapies have become an essential element in the treatment of patients with recurring lymphoma or multiple myeloma. As part of the treatment, the patient’s own T lymphocytes (T cells) are genetically engineered to specifically detect and eliminate cancer cells, with the help of a chimeric antigen receptor (CAR).

The current scientific publication investigates a special case: Nine months after CAR-T cell treatment at Cologne University Hospital, a 63-year-old male patient with multiple myeloma developed a T cell lymphoma, which manifested in the skin and intestine, in addition to the blood. The tumor developed from the genetically engineered T cells used to treat the patient.

This is one of the first documented cases of such a lymphoma after CAR-T cell therapy. The findings from the study help to improve our understanding of the risks involved in the treatment and, if possible, ways to obviate those risks in future. The researchers established that it was not only current genetic changes in the T cells which caused the tumor. Existing genetic changes to the hematopoietic cells of the patient, which had occurred earlier, also played a role. The researchers used state-of-the-art technologies to examine the development of the tumor in detail. Various next-generation-sequencing methods (a high-throughput technology for analyzing DNA and RNA sequences) were employed to analyze the phenomenon. Whole-genome sequencing was used to identify genetic changes, while single-cell RNA sequencing analyzed the transcriptome of the CAR-T cells to explore genes and signaling pathways.

Before this study, these methods had already been established through the close cooperation between the working groups of Prof. Dr Maximilian Merz from Leipzig University Hospital and Dr Kristin Reiche at Fraunhofer IZI. Therefore, this case was analyzed and assessed within an extremely short period of time. “This case provides valuable insights into the evolution and development of a CAR-carrying T cell lymphoma after innovative immunotherapies and highlights the importance of genetic precursors for such a potential side effect”, explains Prof. Dr Merz, senior physician at the hematology, cell therapy, hemipterology and infectiology hospital of Leipzig University Hospital and corresponding author of the study.  

The researchers are now planning further scientific studies to improve our understanding of similar cases and to identify risk factors with greater precision. This aims to predict and prevent such side effects after CAR-T cell therapies, which are increasingly being used in a range of applications.

Original publication in Nature Medicine

Braun T, Rade M, Merz M et al. Multiomic profiling of T cell lymphoma after therapy with anti-BCMA CAR T cells and GPRC5D-directed bispecific antibody. Nat Med (2025). doi: 10.1038/s41591-025-03499-9

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• University Hospital Cologne

Original press release of the University of Leipzig Medical Center

Rare side effect of cancer immunotherapy