FDA Investigating Risk of New Cancers Arising From Gene Therapy

Written by Naveen Athrappully on December 13, 2023. Posted in Current News

A gene therapy treatment used in cancer patients is under scrutiny by the U.S. Food and Drug Administration after the agency received reports of new blood cancers among treated individuals

The treatment, CAR-T, was first approved by the FDA in 2017 and is used in the treatment of blood cancers.

However, the agency has received “reports of T-cell malignancies”—a group of blood disorders—among some of the patients who received CAR-T treatments, according to a Nov. 28 announcement.

The reported malignancies include lymphoma, a cancer of the lymphatic system which includes lymph nodes, the thymus gland, bone marrow, and the spleen.

“Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” the agency said.

In CAR-T treatments, a type of white blood cells called T cells are removed from the blood of a patient. These cells are then genetically engineered to make proteins called chimeric antigen receptors (CAR).

The FDA pointed out that “patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies.”

“In the event that a new malignancy occurs following treatment with these products, contact the manufacturer to report the event and obtain instructions on collection of patient samples for testing for the presence of the Chimeric Antigen Receptor (CAR) transgene,” the agency said.

At present, the FDA has approved six CAR-T products:

• Kymriah from Novartis
• Yescarta from Gilead
• Carvykti from J&J and Legend
• Breyanzi from Bristol Myers Squibb
• Abecma from Bristol Myers Squibb
• Tecartus from Gilead

The risk for developing malignancies applies to all six products, the FDA said.

Surprising Announcement

Medical experts did not expect the FDA’s recent announcement.

Ms. Maus said that the only cases of CAR-T lymphoma or leukemia she heard of were from Australia where the products used a genetic element which was not present in the six CAR-T treatments approved by the FDA.

Bruce Levine, a professor at the University of Pennsylvania Health System, said in a Nov. 29 X post that the FDA report leaves “many questions unanswered,” adding that “colleagues I’ve consulted with are very surprised” by the announcement.

“What was the clinical status of the patients in terms of immunosuppression, prior therapy, conditioning chemotherapy, evidence of prior clonal hematopoiesis?” he asked.

“It’s important to put into context the remote though real risk when compared to conventional chemotherapy that has significant long and short term side effects, including genotoxicity and predisposition to secondary cancers.”

In an interview with The New York Times, Dr. John DiPersio, director of the Center for Genetic and Cellular Immunotherapy at Washington University School of Medicine in St. Louis, said he hasn’t seen “a single one” of his 500 to 700 patients who received CAR-T treatments develop a new T cell cancer.

CAR-T treatments are reserved for patients who would otherwise die without it, he noted.

“They are all going to die and they are all going to die quickly without this treatment. It saves their life … It works in a substantial portion of patients. The benefit is enormous.”

When a patient’s T cells are genetically modified in the CAR-T treatment, a virus is used to slip new genes into the DNA of these cells. As such, when the modified T cells are inserted back into the blood of the patient, it could potentially disrupt other genes and lead to cancer, The New York Times explained.

The Epoch Times reached out to the respective companies for comment.

A Gilead spokesperson told FiercePharma that the company is “confident in the overall safety profile of both Tecartus and Yescarta.” Both treatments have been applied on 17,700 patients, with no evidence linking them with development of new malignancies, the spokesperson stated.

“We have a rigorous process in place to continuously monitor for and report adverse events to regulatory authorities. … We have fully cooperated with the FDA’s request for an analysis of our data related to this inquiry.”

Novartis pointed out that over 10,000 patients have been treated with Kymriah and that the company has not identified its link to any secondary malignancies. Bristol Myers Squibb told the outlet that Abecma and Breyanzi have been used among 4,700 patients, with none of them developing T-cell malignancy.

Data from the FDA Adverse Event Reporting System (FAERS) show that the six products have reported the following adverse events:

• Kymriah—2,470 adverse events, including 2,303 serious cases, 662 deaths, and 504 blood and lymphatic system disorders.
• Yescarta—3,729 adverse events, including 3,551 serious cases, 746 deaths, and 567 blood and lymphatic system disorders.
• Carvykti—408 adverse events, including 251 serious cases, 28 deaths, and 18 blood and lymphatic system disorders.
• Breyanzi—202 adverse events, 172 serious cases, 38 deaths, and 18 blood and lymphatic system disorders.
• Abecma—528 adverse events, 454 serious cases, 60 deaths, and 87 blood and lymphatic system disorders.
• Tecartus—609 adverse events, 570 serious cases, 136 deaths, and 58 blood and lymphatic system disorders.

See more here theepochtimes

Header image: Madalina Vasiliu / The Epoch Times

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