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AE Analysis Finds Low Rate of T-Cell Malignant Neoplasms in CAR T Recipients


Only 11 cases of adverse events (AEs) were reported over a 6-year time frame, the investigators found, following administration of chimeric antigen receptor T-cell therapy (CAR T).

A new retrospective analysis has found fewer than a dozen reports of T-cell–malignant neoplasms (TCMNs) in patients with hematologic malignant neoplasms (HMNs) who have received chimeric antigen receptor T-cell therapy (CAR T).

The findings suggest that CAR T has a favorable risk-benefit ratio, despite fears that the treatment may be associated with a heightened risk of secondary primary malignant neoplasms (SPMNs). The report was published in JAMA Oncology.

The study authors noted that CAR T cells have proven to be a potent immunotherapy option for patients with several refractory HMNs.

“However, concerns regarding SPMNs after CAR T-cell therapy remain and are potentially associated with cumulative exposure to chemotherapeutic agents, prolonged immunosuppression, or insertional mutagenesis,” they wrote.

Indeed, last November, the FDA announced that it was investigating whether BMCA- or CD19-directed CAR T cells were linked with a heightened risk of TCMNs based on reports from clinical trials and postmarketing (AE) event data for approved CAR Ts.

The study authors sought to better understand the potential risk by analyzing data in the FDA’s Adverse Event Reporting System postmarketing surveillance database to see how many cases of SPMNs were reported for the 6 commercially available CAR Ts.

“This retrospective cohort study aimed to ascertain whether a disproportional increase in SPMN and TCMN reporting occurs after CAR T therapy,” they said.

The investigators found 8455 AE reports between September 1, 2017, and September 30, 2023, involving patients who received CAR T in the database. Of those, 386 reports were SPMNs.

“Most SPMNs reported were myeloid neoplasms (220; 57.0%) followed by solid tumors (112; 29.0%),” the authors reported. “TCMNs accounted for 11 [cases] (2.8%).”

They said a disproportionate increase in SPMN reports was observed among patients with HMNs treated with CAR T compared with those that were not (reporting OR, 2.63; 95% CI, 2.34-2.95).

Among the 11 reports of TCMNs, most patients had received CAR T for large B-cell lymphoma (8 patients). Six of those patients had received tisagenlecleucel (Kymriah; Novartis) and 3 patients had received axicabtagene ciloleucel (Yescarta; Kite Pharma). Six of the patients with TCMNs died, the authors noted.

“We found higher-than-expected reporting of SPMN and TCMN after CAR T therapy vs other treatments in patients with HMNs,” the authors said. “Notably, SPMNs were predominantly of myeloid origin, whereas TCMNs were rare.”

Still, they said it is important to note that patients receiving CAR T already have a substantial treatment burden, “including exposure to prior tumorigenic therapies.”

“Additionally, CAR T therapy might facilitate progression of preexisting clonal hematopoiesis to overt myeloid neoplasia,” they added.

Team of researchers | Image Credit: CharlizeD - stock.adobe.com

New research shows a potential favorable risk-benefit profile for CAR T-cell therapy | Image Credit: CharlizeD - stock.adobe.com

Another potential reason for the link, they noted, might simply be that patients who receive CAR T have extended survival and the longer life-span itself might be one reason SPMN development appears higher in this patient group. They said one outstanding question is whether earlier administration of CAR T might lower the risk of SPMNs.

The authors also said these findings need to be considered in a risk-benefit framework, noting that more than 35,000 patients with chemoresistant disease have been treated with CAR Ts. Indeed, even as the FDA announced its intention to investigate the risk associated with CAR Ts, the agency noted that, “the overall benefits of these products continue to outweigh their potential risks for their approved uses.”

The study authors said their findings of fewer than a dozen cases of TCMNs after CAR-T therapy, “suggests a favorable risk-benefit ratio for CAR-T therapies.”

They added, however, that the findings also make clear that careful monitoring and reporting of AEs associated with CAR Twill be important moving forward.


Storgard R, Rejeski K, Perales MA, Goldman A, Shouval R. T-cell malignant neoplasms after chimeric antigen receptor t-cell therapy. JAMA Oncol. Published online April 18, 2024. doi:10.1001/jamaoncol.2024.0662

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