Database Analysis Investigates T-Cell Malignancies After CAR-T

Magdi Elsallab, MD, PhD, of Massachusetts General Hospital, and Moataz Ellithi, MBBCh, of the University of Nebraska Medical Center, discuss their analysis titled, “Second Primary Malignancies After Commercial CAR T Cell Therapy: Analysis of FDA Adverse Events Reporting System (FAERS).”

Following the US Food and Drug Administration (FDA)’s November 2023 announcement on the potential risk of T-cell malignancies after CAR T-cell therapy, the researchers searched the FDA database for the six CAR-T products used to treat blood cancers.

“The idea was to provide some more context because when the FDA released the news about T-cell malignancies, they didn’t share a lot of information about the cases,” Dr. Elsallab said. “We also tried to see if there were any other associations between the T-cell malignancies and other adverse events [AEs] that were reported in the same reports.”

In approximately 12,000 reports of AEs, the researchers found 19 cases of T-cell malignancies that includes four out of the six CAR-T products. The likelihood of reporting a T-cell malignancy after CAR-T was significantly higher in the tisagenlecleucel (tisa-cel) group, Dr. Ellithi noted.

Dr. Elsallab also discussed the limitations of the FAERS database, such as duplicate submissions and the absence of a denominator of the number of products infused into patients, therefore limiting the ability to establish incidence of side effects.

Overall, Dr. Elsallab highlighted the “impressive” response rates of CAR-T cell therapies in clinical trials.

“It’s very important to understand that products will have risks,” Dr. Elsallab said. “The process of approving a product involves weighing the benefits and the risks, and it’s very important to take the cases of adverse events within the bigger context of how important and transformative CAR-T cells have been to a lot of refractory or relapsing hematological malignancies.”