T-cell Malignancies Represent Small Fraction of the Reported Secondary Cancers following CAR-T in the FDA’s Adverse Event Reporting System

Analysis reveals that T-cell malignancies accounted for 0.1% of reports submitted to FDA following CAR T-cell therapy  

(WASHINGTON, March 14, 2024) – An analysis published today in Blood found that secondary cancers following CAR T-cell therapy were reported in 4.3% of CAR-T therapy adverse event reports submitted to the U.S. Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS), with T-cell malignancies representing only 0.1% of the reports. 

CAR T-cell therapies have been approved to treat different hematologic malignancies and involve extracting a patient’s T cells from their blood and modifying them with a gene that targets a specific protein on cancer cells. This modification enables the T cells to find and eliminate cancer cells once reintroduced into the patient's bloodstream. 

In November, the FDA issued a warning about the risk of secondary T-cell malignancies in patients treated with CAR T-cell therapy, requiring some manufacturers to add a boxed warning to their product’s prescribing information. In the analysis, investigators sought to understand the prevalence of T-cell malignancy reports related to CAR-T therapies identified in FDA’s FAERS. 

“We aimed to evaluate the magnitude of secondary cancer reporting to the FDA after CAR-T therapy,” explained Magdi Elsallab, MD, PhD, a researcher at Massachusetts General Hospital, and the study’s co-lead author. “When compared to similar drugs, we observed a slight increase in reporting certain secondary cancers to the FDA after CAR T-cell products.” 

The authors identified 12,394 adverse event reports associated with CAR-T therapy in the FAERS database. Of those reports, 536, or 4.3% listed secondary primary malignancies among other adverse events. Out of the 536 reports, 51.7% and 33% were associated with the specific use of CAR-T products axicabtagene ciloleucel and tisagenlecleucel, respectively.  

The most common secondary cancers observed with CAR T-cell therapy were leukemias, making up 2.7% of all the reports after CAR-T therapy. Skin cancers were the second most common, comprising 0.4% of overall adverse event reports after CAR-T therapy. Seventeen T-cell non-Hodgkin lymphomas were identified in these reports, with the majority being anaplastic large T-cell lymphomas. Two cases of large granular T-cell leukemia also were identified, bringing the total T-cell malignancies in the FAERS database to 19 reports. 

While researchers identified secondary cancer in the FDA reports, they were unable to establish causation based on the data provided by the agency. According to the American Cancer Society, patients undergoing cancer treatment face an elevated risk of developing secondary cancers due to several common treatments, including chemotherapy and radiation. 

“Patients receiving CAR T-cell therapy are often heavily pretreated with other drugs, which can also contribute to the development of secondary cancers,” explained Marcela Maus, MD, PhD, an attending physician at Massachusetts General Hospital. “At this point, the risk of secondary cancers after CAR T-cell therapy cannot be definitively attributed to the CAR T cells as all of these patients received multiple prior chemotherapy agents that are known to elevate the risk of secondary cancers.” 

FAERS relies on voluntary reporting of adverse events, potentially resulting in duplicate submissions from providers, patients, and manufacturers. Additionally, the lack of data on the total number of CAR T-cell therapies prescribed makes it challenging to estimate the incidence of adverse events such as secondary cancers across all CAR-T product usage. 

“We will continue to monitor the data released by the FDA to learn more about CAR-T-associated risks. However, it's crucial to stress that the benefits of CAR T-cell therapies still outweigh the risks for the approved indications,” said Dr. Elsallab. 

Blood (bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available in print and online. Blood is the flagship journal of the Blood journals portfolio (bloodjournals.org) from the American Society of Hematology (ASH) (www.hematology.org).  

Contact:  
Kira Sampson, American Society of Hematology 
ksampson@hematology.org; 202-499-1796