Study Finds Low Secondary Cancer Risk From CAR-T Cell Therapy

A large study conducted by researchers at Stanford Medicine, published in New England Journal of Medicine, has found that the risk of secondary blood cancers after CAR-T cell therapy — a cell-based cancer treatment for intractable blood cancers — is low.

CAR-T cell therapy is an advanced treatment for certain types of cancer. It works by harnessing the body's immune system to fight cancer cells. In the therapy, doctors collect a patient's T cells, genetically modify them to recognize and attack cancer cells, and then infuse these modified cells back into the patient. Once inside the body, these supercharged T cells target and destroy cancer cells, effectively treating the cancer.

In November 2023, the FDA issued a warning about a risk of secondary cancers — particularly blood cancers — that may be associated with CAR-T cell therapy. The warning was preceded by rising concern following reports of patients diagnosed with T cell cancers unrelated to the cancer for which they had been treated.

However, a study involving over 700 patients treated at Stanford Health Care found that the risk of developing a second cancer after CAR-T cell therapy is low, about 6.5% over three years. The researchers used molecular, cellular and genetic analyses to compare all 724 patients’ tumours, their CAR-T cells and their healthy cells at multiple time points before and after CAR-T cell treatment.

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.

In the only instance where a secondary T-cell cancer was fatal, researchers determined it was likely caused by the weakened immune system from CAR-T cell therapy. This allowed existing cancer cells, which were not previously identified, to grow rapidly in the patient's body.

The study’s findings suggested that secondary cancers appearing after CAR-T cell therapy might result from the immune system being weakened before treatment or from the side effects of the therapy itself.

“These findings highlight the importance of studying immune suppression before and after CAR-T cell therapy to understand its role in cancer risk. As CAR-T treatments expand beyond high-risk blood cancers to conditions like autoimmune diseases, this study provides a framework to evaluate their outcomes and clarify their risks and benefits. While CAR-T therapies are lifesaving with minimal risk of secondary cancers, predicting which patients might face higher risks remains a challenge,” said the study authors.

Reference: Emily Mitchell, George S. Vassiliou; T-Cell Cancer after CAR T-Cell Therapy, New England Journal of Medicine, 390, 22, (2120-2121), (2024); /doi/full/10.1056/NEJMe2405538