Case Study Reveals Rare Side Effect of CAR T-Cell Therapy

A new study from researchers at the University of Leipzig Medical Center and collaborators, has discovered a rare but serious side effect of an innovative form of blood cancer therapy in a 63-year-old patient. The side effects arose after the patient underwent chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma. The findings are published in Nature Medicine.

CAR T-cell therapies are essential to some cancer treatments

Cell therapy refers to the transplantation of human cells to either replace or repair damaged tissues and/or cells. CAR T-cell therapy is a cancer immunotherapy in which T cells are derived from a patient's blood and then genetically engineered in vitro to express an artificial receptor, allowing T cells to target specific tumor antigens.

CAR T-cell therapies have become an essential part of treatment in patients with relapsed multiple myeloma and lymphoma – types of malignant blood cancers originating from lymphocytes.

In this study, a 63-year-old patient with multiple myeloma developed T-cell lymphoma in the blood, skin and intestine 9 months after undergoing CAR T-cell therapy. The tumor developed from the genetically modified T cells that were used in the treatment. 

“This is one of the first documented cases of such lymphoma following CAR T-cell therapy,” said Dr. Maximilian Merz, senior physician at the Department for Hematology, Cell Therapy and Hemostaseology at the University of Leipzig Medical Center.

The importance of genetic predispositions in CAR T-cell therapy side effects

Merz and colleagues employed multiple next-generation sequencing techniques to investigate this phenomenon. Whole-genome sequencing identified genetic alterations, while single-cell RNA sequencing examined the CAR T-cell transcriptome to explore gene expression and signaling pathways.

The researchers discovered that it was not just current genetic alterations of the T cells that caused the tumor, but also pre-existing genetic changes in the patient’s hematopoietic cells played a role. 

The close collaboration between clinicians and basic scientists in the field of CAR T-cell therapy allowed for the case to be analyzed in a very short time.

“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,” Merz highlighted.

Attempting to better understand the risks

The researchers are planning future studies to better understand similar cases and identify risk factors, intending to be able to predict and prevent such side effects after CAR T-cell therapies.

“It is important to create a real, data-based awareness of the rarity of this complication, at far less than one percent, and the mechanisms by which it occurs,” said Dr. Marco Herling, senior physician specializing in internal medicine, hematology and oncology at the University of Leipzig Medical Center.

“The findings of this study will help us to better understand the risks associated with the therapy and possibly prevent them in the future,” said Merz.

Reference: 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. 2025:1-9. doi: 10.1038/s41591-025-03499-9

This article is a rework of a press release issued by Universität Leipzig. Material has been edited for length and content.