Study Uncovers Rare Adverse Effect of CAR-T Cell Therapy for Blood Cancer

A collaborative research effort involving experts from the University of Leipzig Medical Center, the Fraunhofer Institute for Cell Therapy and Immunology (IZI), and the University Hospital of Cologne has led to significant findings regarding a rare but serious side effect associated with CAR-T cell therapy, an innovative treatment for blood cancers such as multiple myeloma and lymphoma. The study has been published in the prestigious journal Nature Medicine.

CAR-T cell therapy represents a groundbreaking approach wherein a patient's T lymphocytes are genetically engineered to identify and destroy cancer cells. This method has been increasingly utilized for patients whose blood cancers have relapsed. However, the recent research highlights a case involving a 63-year-old multiple myeloma patient who developed T cell lymphoma in the blood, skin, and intestines nine months post-treatment. Alarmingly, the lymphoma originated from the genetically modified T cells that were intended to combat the cancer.

The project was spearheaded by Professor Marco Herling, a leading physician at the University of Leipzig Medical Center, alongside Dr. Till Braun, who heads a research group at the University Hospital of Cologne. Both have extensive expertise in the challenging treatment of T cell lymphomas, making their insights particularly valuable.

According to Professor Maximilian Merz, who served as the study's corresponding author, this case marks one of the first documented instances of T cell lymphoma developing after CAR-T cell therapy. The research aims to deepen the understanding of the associated risks of this treatment, with the hope of preventing such occurrences in the future.

In their investigation, the researchers identified that the tumor's emergence was not solely due to genetic alterations in the modified T cells; pre-existing genetic changes in the patient's hematopoietic cells also contributed to the malignancy. Utilizing advanced technologies, the team conducted a thorough analysis of the tumor's progression.

The researchers employed various next-generation sequencing techniques, including whole-genome sequencing to reveal genetic alterations and single-cell RNA sequencing to examine the CAR-T cells' transcriptome. These methodologies were developed collaboratively between the groups led by Professor Merz and Dr. Kristin Reiche at the Fraunhofer IZI, underscoring the importance of teamwork between clinicians and basic scientists in expediting the analysis.

The University of Leipzig Medical Center is recognized as a leading institution in CAR-T cell therapy for multiple myeloma and T cell lymphoma, facilitating rapid insights into such complex cases.

Professor Merz emphasized that this specific case offers vital information regarding the development of CAR-T cell lymphoma following advanced immunotherapies and underscores the significance of genetic predispositions in potential side effects.

Future research endeavors are planned to explore similar cases and identify risk factors associated with CAR-T cell therapies, which are increasingly being adopted worldwide. A secondary paper from the same research team has been submitted to the journal Leukemia, summarizing this case along with nine other global instances of T cell lymphoma related to CAR-T therapy.

Typically, the peer review process for scientific papers can extend over several weeks or months. However, the manuscript concerning this study was accepted within just a day. Professor Herling noted the importance of fostering an informed understanding of this rare complication, which occurs in less than 1% of patients, and elucidating the mechanisms that lead to its development.