FDA warns of secondary cancer risk associated with CAR-T cancer treatment -WIW
The US Food and Drug Administration has issued a new warning about the potential risk of secondary cancers in cancer patients treated with an immunotherapy called a chimeric antigen receptor T-cell or CAR-T cell. therapy
The FDA sent notices to several manufacturers of these drugs this week and last week, requiring them to include a “boxed warning” in the prescribing information for the products. A number of T-cell malignancies, some of which resulted in hospitalization and death, have occurred after BCMA- and CD19-directed genetically engineered autologous T-cell immunotherapy, the warnings state.
“We want to emphasize that the overall benefits of these products continue to outweigh their potential risks,” FDA spokeswoman Carly Pflaum said in an email Wednesday.
As of Monday, the agency had received 25 reports of T-cell malignancy after CAR-T-cell immunotherapy, according to the email.
T cells, a type of white blood cell, are the backbone of CAR-T therapies. They work by harnessing a patient’s T cells, modifying them in the laboratory to attack cancer cells, and then returning the modified T cells to the patient via infusion.
Currently approved CAR-T cell immunotherapies include Abecma, Breyanzi, Carvykti, Kymriah, Tecartus, and Yescarta. Kymriah, the first FDA-approved CAR-T cancer treatment for leukemia, was approved in 2017. Initial approvals for these treatments included an FDA requirement for 15-year follow-up studies to assess long-term safety and secondary risk. cancers after treatment.
Previously, the risk of secondary malignancies was listed as a “categorical warning” in the United States on prescribing information for these CAR-T therapies.
“The FDA considers that a serious risk of T-cell malignancy applies to all BCMA- and CD19-directed genetically engineered autologous T-cell immunotherapies,” the FDA said in a press release Tuesday. “The letters urge the manufacturers of each of these authorized products to update the packaging to include risk information and to update the packaging for those products to identify an increased risk of cancer, including certain types of immune system cancer. .”
According to the FDA, patients and those in clinical trials receiving this treatment should be monitored “for life” for new malignancies. If a new malignancy develops after treatment, healthcare providers are advised to contact the manufacturer to report the incident and obtain instructions for obtaining a patient sample for testing.
“An individual patient should not be overly concerned about the risk of this particular treatment-induced T-cell lymphoma after CAR-T-cell therapy, the risk appears to be very small,” said Dr. Joshua Brody, director of lymphoma immunotherapy. . program at Mount Sinai’s Tisch Cancer Institute, which was not covered by the FDA warning, wrote in an email Wednesday. “The real impact of this new safety label is that it forces CAR-T developers to develop even safer versions for future patients.”
The FDA announced in November that it is investigating the risk of secondary cancers with certain CAR-T cell therapies.
By the end of last year, the agency had received 22 cases of different types of T-cell malignancies that may be linked to CAR-T therapy, said Dr. Peter Marks, director of the Center for Biologics Evaluation and Research. from the FDA. in a presentation at the Alliance for Regenerative Medicine this month.
He added that more than 27,000 people have been treated with his CAR-T therapy in the United States.
“So the number of individual cases, when we are dealing with tens of thousands of people, is not too much of a concern for us now in this malignant environment,” he said.
“We have provided preliminary guidance here on what we are asking for: long-term follow-up; we are asking providers, if they see a new T-cell malignancy, to contact the manufacturers and us to get the data we need to understand the frequency of these events .” But make no mistake, the overall risk-benefit profile is still incredibly helpful,” Marks said. “Over the coming months, as we learn more, we’ll adjust and update our information.” how oncologist Dr. Eric Smith treats his patients. , he said.
“The benefits of CAR-T cell therapies continue to outweigh the risks to our patients,” Smith, director of translational research on immune-effector cell therapies such as CAR-T cell therapies at the Dana-Farber Cancer Institute. , said Wednesday. via email.
“These cases and the potential for secondary cancers are and should be taken seriously, but they do not significantly affect FDA-approved regimens. Patients who require this treatment are often at high risk of dying from their current condition. cancers and CAR T-cell therapies have changed the extent and duration of response in patients with these relapsed or refractory blood cancers,” he said. “Given the low incidence of these secondary malignancies, it is important that we continue to offer CAR T-cell therapy to our patients who need it.”
Dr. Mikkael Sekeres, chief of hematology at Sylvester Comprehensive Cancer Center in Miami, said he doesn’t think patients should worry more than they should about the risks associated with CAR-T therapy. other anti-cancer treatments.
“Unfortunately, when we give cancer treatment, there are no free rides – any effective cancer treatment can have side effects. CAR T-cell therapies are often offered to people with lymphoma, leukemia or multiple myeloma who have relapsed after conventional treatment, and they work really, really well,” he said in an email Wednesday.
“I continue to recommend CAR. T-cell therapies to my patients, as I have always done, and include a discussion of the risk of a second cancer, as I do with other cancer treatments,” Sekeres said. “I applaud the FDA for including the additional risk in the safety label for CAR-T cells.
