Secondary T-Cell Cancers After CAR T: Rare, Real, and Worth Watching

Chimeric antigen receptor (CAR) T-cell therapy had changed the outlook for many patients with blood cancers. The therapy is not risk free, and one of its rarest complications, T-cell cancers arising from the engineered cells themselves, has drawn attention and a label warning. Kerry Rogers, MD, a hematologist-oncologist and associate professor at The James/The Ohio State Comprehensive Cancer Center, says the concern is legitimate. She also says it should not steer patients away from a treatment that may help them.

Rogers explained that the concern has a clear biological basis. CAR T cells are made by engineering a patient’s own T cells, mostly using a virus. Altering a cell’s DNA can induce mutations or other problems. The engineered cells can then behave like a cancer and grow out of control. Because the cells are autologous, meaning they come from the patient’s own body, the immune system is unlikely to attack them as foreign. Tumors made of CAR T cells have been reported, Rogers said, and similar events have been seen with other cell therapy products. That is why close monitoring and the label warning matter, she added.

Even so, she stressed the event is “extremely rare.” It is not something she spends much time worrying about or counseling patients on, because it occurs too seldom to outweigh the benefit of treatment. The patients with chronic lymphocytic leukemia (CLL) for whom she recommends CAR T-cell therapy generally lack other options that would keep them alive and healthy for years. The main alternative, donor stem cell transplant, carries more complications. Rogers put the risk in content by comparing it with other, more common dangers.

“I worry way more about morbidity and mortality from cytokine release and neurotoxicity than I do about these rare T-cell cancers,” she said.

Her bottom line for patients weighing the treatment is direct. “I do not think that the small risk negates the benefits.” In her view, the possibility of a rare secondary cancer should not be a deciding factor for patients considering CAR T-cell therapy.