Benefits Outweigh Risks as FDA Inspects CAR-T Cell Therapy-Related Cancer

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The FDA announced rare instances of secondary diseases or cancers from CAR-T cell therapy, though this is not the first time that oncology treatments have been associated with secondary diseases.

Note: This is a developing story. Check back later on curetoday.com to read more.

The Food and Drug Administration (FDA) recently announced that it received reports of T-cell malignancies — including CAR-positive lymphoma — in patients who have been treated with BCMA- or CD-19-directed autologous CAR-T cell therapies.

CAR-T cell therapy is a type of treatment that engineers patients' immune systems to fight cancer.

Autologous CAR-T cell therapy is a new and oftentimes curative approach for certain types of blood cancers. The treatment involves extracting a patient’s immune T cells, re-engineering them to find and fight cancer, growing the number of engineered cells and then infusing the T cells back into the body.

The first CAR-T cell therapy was approved in August 2017, and since then, the treatment modality has been touted as a “one-and-done” and potentially curative option for certain types of blood cancers.

However, now the FDA is stating that data from clinical trials and/or postmarketing side effect data sources are showing that a small number of patients who underwent this type of treatment were diagnosed with secondary T-cell malignancies, which are diseases of the immune T cells.

In a Nov. 28, 2023, statement, the FDA wrote, “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.”

Clinicians Comment on T-Cell Malignancy Risk from CAR-T Cell Therapy

Since the statement, experts have been commenting on the news via social media.

“I have treated hundreds of patients with CAR-T cell therapy: all had a life-threatening cancer, and many have been cured. A few cases of a possible side effect are important and should be further studied, but the benefits far outweigh the potential risk,” Dr. Jason Westin, professor, Director of Clinical Research and Section Chief of Aggressive Lymphoma at The University of Texas MD Anderson Cancer Center in Houston, said on X (formerly known as Twitter).

Another expert, Dr. Rahul Banerjee, assistant professor at UW Medicine Fred Hutch Cancer Center, who specializes in bone marrow and blood stem cell transplantation and cellular immunotherapies for blood cancers, said that he will not be changing his treatment of patients until the FDA publishes more data on the incidence of secondary T-cell malignancies, stating that CAR-T cell therapy has already saved thousands of lives.

Cancer-Causing Cancer Treatments Is Not a New Phenomena

Banerjee also mentioned on X that other blood cancer treatments also carry a risk for T-cell lymphomas.

“Unfortunately, the risk of T-cell lymphoma from prior (Revlimid [lenalidomide]), prior (autologous stem cell transplant), prior (Bendeka [bendamustine]), is very real with or without CAR-T. (There were) no case controls here…”

This is not the first instance of oncology treatments potentially causing other cancer diagnoses. The National Cancer Institute reported that nearly 20% of cancers diagnosed occur in people with a previous cancer history — and some of those diagnoses are a result of their prior treatment with modalities such as radiation or certain hormone therapies.

Next Steps for CAR-T Cell Therapy-Related Cancers

There are currently six FDA-approved CAR-T cell therapies that are directed at either BCMA or CD19, both proteins that contribute to cancer cell growth:

Abecma (idecabtagene vicleucel)
Breyanzi (lisocabtagene maraleucel)
Carvykti (ciltacabtagene autoleucel)
Kymriah (tisagenlecleucel)
Tecartus (brexucabtagene autoleucel)
Yescarta (axicabtagene ciloleucel)

The initial approvals of all these drugs included requirements per the Federal Food, Drug and Cosmetic Act to conduct 15-year follow-up studies assessing the safety and risk of secondary diseases that may occur after treatment. Now, the FDA is also stating that patients who received CAR-T cell therapy — be it in clinical trials or in the traditional cancer treatment setting — should undergo lifelong monitoring for new malignancies.

The agency wrote, “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.”

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