A case study of a 63-year-old male with early relapse of multiple myeloma (MM) indicated that treatment with a chimeric antigen receptor (CAR) T-cell therapy and talquetamab induced peripheral T-cell lymphoma (PTCL) in the blood, skin, and intestines.
The case was presented by Till Braun, MD, of the University Hospital Cologne in Germany, and published in Nature.
The patient received ciltacabtagene autoleucel and talquetamab and experienced the secondary malignancy nine months after CAR-T therapy.
“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,” Maximilian Merz, MD, an author of the paper, said in a press release about the case.
The researchers used whole-genome sequencing to identify genetic alterations, as well as single-cell RNA sequencing to analyze the transcriptome of the CAR-T cells to investigate genes and signaling pathways.
The researchers indicated that genetic alternations of the T cells caused the tumor, as did preexisting genetic changes in the patient’s hematopoietic cells.
They plan to further study this occurrence to better understand similar cases and identify potential risk factors.
“This case highlights the evolution of a CAR-carrying [PTCL] following CAR T-cell and bispecific T-cell engager therapy, offering critical insights into the clonal evolution from a predisposed hematopoietic precursor to a mature neoplasm,” the authors concluded.
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. Nature. 2025. Epub ahead of print. doi:10.1038/s41591-025-03499-9
