Car-T Therapy May Increase Risk of Certain Cancers

The risk of CAR-T therapy is known, but statistically very rare, and the benefits of the treatment still outweigh those potential downsides, Dr. Wael Harb, board-certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast and Saddleback Medical Centers in Orange County, CA, told Healthline.

“This risk is associated with the use of a virus (usually a lentivirus) to integrate the gene encoding the CAR into the T cells’ DNA. The concern is that this integration could potentially activate oncogenes if it occurs near cancer-associated genes,” Harb said. “The overall benefits of CAR T-cell therapy, especially in cases of blood cancers where patients have few other options, are still considered to outweigh these risks.”

While the FDA warning will raise some concerns for doctors and physicians, it’s still not clear that the rare blood cancers in some people were directly caused by the therapy, according to Dr. Naveed Wagle, neuro-oncologist at Pacific Neuroscience Institute in Santa Monica, CA and Associate Professor of Translational Neurosciences at Saint John’s Cancer Institute in Santa Monica, CA.

“CAR-T therapy is still very early in its clinical development. The approval of these medications was warranted based on the clinical trial efficacy they showed,” Wagle said. “The new data in post-approval use is correlative and does not show a direct causal relationship. However, it does raise concerns and warrants close surveillance.”

Harb echoed the need for monitoring, pointing out that the FDA warning doesn’t suggest that CAR-T therapy should be suspended.

“Given the transformative impact of this therapy in treating blood cancers, especially in patients with relapsed or refractory disease, it’s likely that many doctors will continue to consider it a valuable treatment option,” Harb said. “The actual impact on the use of CAR T-cell therapy will depend on individual assessments of risk versus benefit, further findings from ongoing investigations, and possible updates to treatment guidelines or protocols.”

According to the National Cancer Institute, CAR-T therapy leads to long-term survival in only roughly half of people who undergo it, and the cost — hundreds of thousands of dollars — can be prohibitive. There are still multiple forms of treating cancer, although they need to be tailored to a person’s needs through consultation with their physician — but there are still risks to those as well, Harb said.

“These include traditional treatments like chemotherapy, radiation, and small molecule drugs, each of which also carries its own risks and benefits. For multiple myeloma patients, treatments such as alkylators, immunomodulatory drugs, and autologous stem cell transplantation are alternatives, though they too are associated with a risk of secondary cancers,” Harb said. “The choice of treatment should be a decision made in consultation with healthcare providers, considering the individual patient’s situation, the type of cancer, previous treatments, and overall health.”

The FDA has ordered the manufacturers of six CAR-T therapy drugs to put a warning on their prescription information that a rare form of blood cancer is a risk of the treatment.

CAR-T therapy, which is used to treat blood cancers like leukemia, multiple myeloma and lymphoma, involves taking cells from a person’s body, altering them genetically to bind to the antigens of cancer cells, and then reinfusing them into the person.

Statistically, the risk of rare blood cancer from CAR-T therapy is low, but physicians say more monitoring and testing is needed.