Pleading the CAR-T Case

Scientists from Stanford University suggest the risk of secondary blood cancers after CAR-T cell therapy is low despite a recent FDA warning that shook-up the industry. The study, which consisted of 700 cancer patients who received the immunotherapy, found that just over 6 percent experienced complications across a three year monitoring period – a number similar to that of patients who receive stem cell transplants.

The general concern surrounding CAR-T therapy is that, if the genetic engineering is imprecise, the T-cells meant to attack a person’s cancer might instead become cancerous themselves. However, the researchers found no evidence that the T-cells responsible for some patients’ secondary cancers were the T-cells that had been engineered for CAR-T cell therapy. They instead noted that the T-cells were distinct on both genetic and molecular levels.

Though there was a sole case of fatal secondary T-cell cancer, the team believe it was because of immunosuppression caused by CAR-T cell therapy – rather than the CAR-T cells. The patient also had a history of autoimmune disease prior to a cancer diagnosis. 

“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,” said Ash Alizadeh, Professor of Medicine and Member of the Stanford Cancer Institute, in a press release.

The results suggest that secondary cancers might actually be prompted by chemotherapy (prior to CAR-T therapy) that suppresses a person’s immune response. “[Our] study could serve as a blueprint for how to capture and characterize the outcomes of CAR-T therapies so we can develop a very clear understanding of their risks and benefits,” said Alizadeh. “These are lifesaving therapies that come with a very low risk of secondary cancers. The challenge lies in how to predict which patients are at higher risk, and why.”

Indeed, their findings may alleviate some of the concerns sparked by the FDA’s “black box” warning, but it may also help researchers and clinicians identify prospective CAR-T cell therapy recipients who are at increased risk of secondary cancers. Though patients are unlikely to reject life-saving treatment because of a small risk of future cancer, they could benefit from closer monitoring post-therapy or comprehensive screening for other cancers before starting CAR-T cell treatment.

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