Risk of secondary cancer with CAR-T treatment is low, large study finds

In 2023, the US Food and Drug Administration (FDA) issued a warning about the risk of certain secondary cancers associated with CAR-T cell therapy, and now a study of 724 patients has concluded that this risk short.

The findings, which specifically address the risk of secondary blood cancers, were published in the New England Journal of Medicine in a paper signed by Stanford University scientists: “This large study confirms that the risk after CAR T cell therapy is low, despite the FDA warning.”

This therapy, as a method of treating oncology, appeared on the scene in 2017 for the treatment of incurable blood cancer. It is now widely used for these purposes, and experiments are being conducted – even in animals – with solid tumors and even diseases such as chronic asthma.

CAR-T cell treatment, whose full name is chimeric antigen receptor T-cell therapy (abbreviated CAR-T), involves modifying immune T-lymphocytes (white blood cells) in a sick person’s laboratory so that they become functional. to recognize and fight tumor cells.

In November 2023, the FDA announced that it was assessing the risk that these treatments may in some cases cause tumors secondary to the treatment, especially blood cancers.

However, a study of more than 700 patients treated at Stanford Medical Center suggests the risk is small: about 6.5% within three years of therapy, the statement summarizes.

In the only case of fatal secondary T-cell cancer, the researchers found that it was likely due to immunosuppression caused by CAR-T cell therapy rather than CAR-T cell therapy.

The weakened immune system allowed pre-existing but previously undetected cancer cells to begin to grow rapidly in the patient’s body.

“We wanted to understand this rare case, so we took a close look at all the patients who received CAR-T cell therapy at Stanford and looked at this single case in unusual depth,” explains Ash Alizadeh.

To do this, the team compared the protein levels, RNA and DNA sequences of individual cells across many tissues and at different time points to determine that the therapy did not cause lymphoma in this patient, but that it was already developing in his body.

The study’s findings, the authors say, could “ease” some of the concerns raised by the FDA’s warnings on drug labels and, most importantly, help researchers and clinicians identify potential CAR-T cell therapy recipients at increased risk of developing secondary cancers. .

They can be monitored more closely after receiving therapy, or they can be screened more closely for other cancers before starting CAR-T cell treatment.

“The study describes a rare event in a patient receiving CAR-T therapy and provides very useful information for clinicians. They can monitor such conditions and potentially identify secondary tumors earlier and treat them better,” concludes Metin Ozdemirli from Georgetown University.

According to Joaquín Martínez López, head of the hematology service at the 12 October Hospital (Madrid), “this is a retrospective work with the limitations it entails and confirms the data previously presented by the University of Pennsylvania.”

However, the molecular study performed on the two tumors was “high quality,” says Martinez, who was not involved in the work.

“Although follow-up should be longer, it confirms that CAR-T therapy does not currently lead to the development of T-cell lymphomas secondary to it, but rather represents a different entity. The benefits of this treatment far outweigh the risks,” he told Science magazine. Media Center is a platform for scientific journalistic resources.