medwireNews: Analysis of pharmacovigilance data has revealed a higher-than-expected reporting of second primary malignant neoplasms (SPMNs) in hematologic cancer patients receiving chimeric antigen receptor (CAR) T-cell therapy versus other treatments.
The study also found a significant over-reporting of T-cell malignant neoplasms (TCMNs) after receipt of CAR T-cell therapy, but the absolute number of cases was small, which “suggests a favorable risk-benefit ratio,” say the researchers.
Nevertheless, they stress that “the findings underscore the need for diligent monitoring and reporting of long-term adverse effects of CAR-T therapy.”
Roni Shouval (Memorial Sloan Kettering Cancer Center, New York, USA) and co-workers queried the FDA Adverse Event Reporting System (FAERS) postmarketing surveillance database and identified 8,964,773 AE reports between September 2017 and September 2023. Of these, 8455 (0.1%) involved patients treated with one of six commercially available CAR T-cell products, and 386 (4.6%) of the reports were SPMNs.
The majority (57.0%) of reported SPMNs were myeloid neoplasms, while 29.0% were solid tumors. There were just 11 cases of TCMNs, accounting for 2.8% of the SPMN reports.
There was a disproportional increase in SPMN and TCMN reporting among patients with hematologic cancers who received CAR T-cell therapy versus those who did not, with significant reporting odds ratios of 2.63 and 3.03, respectively.
“The high frequency of myeloid neoplasms should be interpreted in the context of the substantial treatment burden in patients receiving CAR-T therapy, including exposure to prior tumorigenic therapies,” caution Shouval and colleagues in a research letter published in JAMA Oncology.
“Additionally, CAR-T therapy might facilitate progression of preexisting clonal hematopoiesis to overt myeloid neoplasia,” and “[e]xtended survival also allows more time for SPMN development,” they continue.
The team writes in conclusion that “[i]t remains to be determined whether administration of CAR-T therapy in earlier lines mitigates this multifactorial risk of subsequent second malignant neoplasm,” and also whether the TCMNs “are causally associated with genetically modified CAR-T, which requires additional insertion-site analysis.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group