Some forms of blood cancer, such as multiple myeloma and lymphoma, are malignant diseases originating from immune cells, specifically lymphocytes. In recent years, CAR-T cell therapies have emerged as a crucial treatment option for patients with relapsed lymphoma or multiple myeloma. This therapy involves genetically modifying the patient’s own T lymphocytes (T cells) to recognize and eliminate cancer cells using a chimeric antigen receptor (CAR). A unique case has been highlighted in a recent scientific publication.
A 63-year-old patient with multiple myeloma developed T cell lymphoma in their blood, skin, and intestine nine months after undergoing CAR-T cell therapy at the University Hospital of Cologne. This tumor originated from genetically modified T cells used during the treatment. The collaborative project leaders, Professor Marco Herling of the University of Leipzig Medical Center and Dr. Till Braun of the University Hospital of Cologne, are renowned experts in understanding rare yet challenging-to-treat T cell lymphomas.
“This is one of the first documented cases of such lymphoma following CAR-T cell therapy,” says Professor Maximilian Merz, who led the current study alongside Professor Marco Herling. “The findings from this research will help us better understand the risks associated with this therapy and potentially prevent them in future treatments.”
The researchers discovered that genetic alterations both in the modified T cells and pre-existing changes in the patient’s hematopoietic cells contributed to tumor development. They utilized advanced technologies to thoroughly study tumor evolution, including various methods of next-generation sequencing—a high-throughput technology for analyzing DNA and RNA sequences.
Whole-genome sequencing was employed to identify genetic alterations, while single-cell RNA sequencing analyzed the transcriptome of CAR-T cells to investigate genes and signaling pathways. These techniques were previously developed through close collaboration between Professor Merz’s research group at the University of Leipzig Medical Center and Dr Kristin Reiche’s team at Fraunhofer IZI.
The collaborative efforts between clinicians and basic scientists in the field of CAR-T cell therapy enabled a swift analysis of this case. The University of Leipzig Medical Center is one of Europe’s leading centers for treating multiple myeloma with CAR-T cells and T cell lymphoma.
“This case provides valuable insights into the emergence and development of CAR-bearing T-cell lymphomas following innovative immunotherapies, emphasizing the significance of genetic predispositions in potential side effects,” says Professor Merz, a Senior Physician at the Department for Hematology, Cell Therapy and Hemostaseology at the University of Leipzig Medical Center.
The researchers are planning further scientific studies to better understand similar cases and identify risk factors. Their aim is to predict and prevent such adverse effects following CAR-T cell therapies, which are increasingly utilized globally. The relevance of secondary tumors after CAR-T cell therapy has also been emphasized in a second scientific paper submitted by the same research team.
This manuscript was accepted for publication within a day from submission to the high-impact journal Leukemia, where it systematically summarizes this patient case and nine other recently published cases of T-cell lymphoma resulting from CAR-T cells worldwide. The researchers highlight the importance of creating data-driven awareness about the rarity of this complication—far less than one percent—and understanding how it occurs.
This research was funded by EU project CERTAINTY and the Translational Research Award of the International Myeloma Society, underscoring its significance in advancing knowledge and improving patient outcomes.
