Jun 12 2024Stanford Medicine A large study by researchers at Stanford Medicine has found that the risk of secondary blood cancers after CAR-T cell therapy -; a cell-based cancer treatment that exploded on the scene in 2017 as a treatment for intractable blood cancers -; is low, despite a Food and Drug Administration warning.
We wanted to understand this one rare case, so we analyzed all the patients treated with CAR-T cell therapy at Stanford with wide breadth and studied this single case extraordinary depth. We compared protein levels, RNA sequences and DNA from single cells across multiple tissues and time points to determine that the therapy didn't introduce the lymphoma into this patient; instead it was already brewing in their body at very low levels.
In CAR-T cell therapy, immune cells called T cells are isolated from a patient and genetically engineered to more efficiently seek out and kill cancer cells. To do so, researchers introduce a custom-made gene into the T cells' DNA. This gene encodes instructions for a protein called a chimeric antigen receptor that recognizes and binds to cancer cells; when the protein is made by the T cells and affixed to their surfaces, they become efficient cancer-killing machines.
The researchers analyzed the outcomes for 724 people treated with CAR-T cell therapy at Stanford Health Care between 2016 and 2024. Among those people, the incidence of secondary blood cancers approached 6.5% over a median of three years of follow-up, which is roughly similar to patients who underwent stem cell transplantation rather than CAR-T cell therapy to treat their cancers.
The analysis found no evidence that the T cells responsible for the patient's second cancer were the T cells engineered for the CAR-T cell therapy -; they were molecularly and genetically distinct. However, both sets of T cells were infected with a virus known to play a role in cancer development. Furthermore, the patient had a history of autoimmune disease in the years prior to their first cancer diagnosis.
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