A recent in-depth study of a patient’s second cancer following CAR-T therapy for the first cancer is offering valuable insights for oncologists and pathologists. This analysis aims to provide guidance on the clinical and pathological aspects of a CAR-T related second cancer.
The discovery was published on June 13, 2024, in the New England Journal of Medicine.
Many people consider CAR-T therapy to be a new and promising treatment for blood cancers. This therapy involves using a patient’s own cells, specifically T cells from the immune system, which are collected and modified in the laboratory to create proteins called chimeric antigen receptors (CARs) on their surface. These CARs are capable of identifying and binding to specific proteins present on the surface of cancer cells. CAR-T therapy is primarily used for the treatment of blood cancers such as multiple myeloma, the same type of cancer that the patient in the case study had when undergoing treatment.
“The importance of CAR-T treatment and its impact on cancer patients is considerable,” states the primary author of the study, Dr. Metin Ozdemirli, who is a professor of pathology at Georgetown University School of Medicine and also serves as an attending physician and director of Hematopathology and Hematology Laboratories at MedStar Georgetown University Hospital. “Our case study details a rare occurrence in a patient who underwent CAR-T therapy and offers valuable information for physicians treating patients with this method. With our findings, physicians can be alert for similar conditions and potentially identify secondary issues associated with CAR-T.”The goal of CAR-T therapy is to target and eliminate cancer cells in the body. This treatment has shown promise in treating certain types of cancer, but there have been rare cases of second cancers, such as lymphomas, occurring after CAR-T cell therapy. The exact cause of how CAR-T cells can become lymphomas is still unknown, but it is possible that the cells may have had lymphoma-causing mutations when they were initially collected from the patient. Alternatively, the mutations could have occurred during the preparation of the CAR-T cells outside of the patient’s body. Despite these rare occurrences, the overall benefits of CAR-T therapy in treating cancer remain promising, and efforts are underway to detect and manage any potential second cancers earlier and more effectively.or the CAR-T cells may have acquired the mutations after they were given back to the patient; or any combination of these circumstances.
Four months after receiving CAR-T therapy, the patient in the case study developed progressively worsening non-bloody diarrhea and lost 12 pounds. Results of bloods tests led to an endoscopic exam revealing ulcerations in the duodenum, the first part of the small intestine. The patient received treatment, but symptoms persisted, resembling an autoimmune disease. After numerous additional tests, biopsies taken revealed the culprit — indolent T-cell lymphoma of the gastrointestinal tract.
Upon initial examination, it was believed to be a typical case, but further examination at the molecular level revealed that it was actually a case that tested positive for CAR-T.
According to Ozdemirli, this particular case study indicates that doctors treating patients with CAR-T therapy should always consider the possibility of new cancers and autoimmune issues arising from the treatment. “Identifying potential issues in advance makes it easier to address them sooner,” he explains.
Ozdemirli also notes, “One notable discovery here is the specific type of cells that survived the initial treatment and subsequently became cancerous. The immune cells obtained from patients for the creation of the CAR-T therapy are not all the same type of cell.”The cells in question are a combination of various types, including a specific type called a helper T cell, which is a crucial component of the body’s defense against infections and, in this case, unexpectedly contributed to the problem. Although rare, it is possible for a second cancer to develop after undergoing chemotherapy or radiation therapy. Just like any other tissue in the body, CAR-T cells also carry this risk. However, there is currently no evidence to suggest that the process of preparing the CAR-T cells outside the body increases this risk. The researchers also highlight the potential future diagnostic and treatment benefits of switchable cells.In the realm of cell therapies, there is potential for patients to use a drug to adjust the level of CAR-T cell activity on a daily basis. This could lead to a decrease in harmful side effects. Moving forward with this research and gaining more knowledge is a crucial next phase for the researchers.
