Scientists use harmless viruses, which have a natural ability to invade cells, to carry and insert new genetic material. However, the potential for these viruses to accidentally cause other cancers has long been considered a theoretical risk. The FDA said in the notice that the use of these viruses may be involved in the development of second cancers in patients.
The downside to using viruses is that they tend to drop their genetic cargo at random locations within a person’s genome. Depending on where this new genetic material is integrated, nearby cancer genes may be activated. “The concern is that the new genetic material injected into a patient’s T cells could somehow induce cancer in those cells, perhaps depending on where in the DNA it is inserted.” Mr. Porter says.
Because of this risk, the FDA now requires that patients receiving CAR-T cell therapy be monitored for 15 years after treatment. In a notice Tuesday, the agency suggested that “patients and clinical trial participants treated with these products should be monitored throughout their lives for new malignancies.”
Maxim Mamonkin, an associate professor of pathology and immunology at Baylor College of Medicine who is involved in several clinical trials of CAR-T cell therapy, has demonstrated genetic engineering in dozens of patients treated at the university. He stated that he is not aware of any cases in which T cells that have been treated have turned into cancer. . But no treatment is risk-free, he says. “That doesn’t mean it’s impossible,” he says. “We cannot rule out the possibility that the CAR gene is misplaced in the genome by mere chance.”
Another explanation is that previous cancer treatments, including chemotherapy and radiation, were responsible for the patient’s new-onset T-cell cancer. These treatments kill cancer cells, but they also damage the DNA of healthy cells. Doing so can cause changes in cells that can later lead to cancer.
“Cancer is often more than just a single mutation or multiple lesions,” Porter says. “That means previous chemotherapy or radiation treatments can damage the DNA and make those cells more susceptible to infection. If something else happens, it’s already on its way to becoming a cancer cell. Become.”
A spokesperson for Novartis, which makes Kymriah, said 10,000 patients have been treated with the therapy since its approval in 2017. The company has so far seen no evidence that changes its confidence in the therapy’s risk-benefit profile. “As part of ongoing safety monitoring, Novartis has not determined a causal relationship between Kymriah and secondary malignancies,” a spokesperson told WIRED in an email.
A representative for Bristol-Myers Squibb, which makes two approved CAR-T cell therapies, Avekuma and Breyanzi, wrote that the company is aware of the FDA investigation. More than 4,700 patients have received this treatment in research trials or as a commercial product. “To date, BMS has not observed any cases of CAR-positive T-cell malignancies, so we have not found a causal relationship between our products and secondary malignancies,” a spokesperson told WIRED in an email. Ta.
Johnson & Johnson, which makes another FDA-approved treatment called Carvicti, said through a spokesperson that the company is committed to the health and safety of its patients. . “We are sharing the data with the FDA and are collaborating with them as they evaluate the safety signal of this newly identified class effect,” a spokesperson told WIRED in an email. Ta. More than 2,000 patients have been treated with Carvykti, they wrote.
In a statement yesterday, the FDA said, “The benefits of these products continue to outweigh the potential risks.”
Porter agrees. “Obviously this is concerning and we need more information,” he says. “But it is likely to be a rare phenomenon.”