Study reveals increased risk of secondary cancers linked to CAR-T cell therapy treatments worldwide
A groundbreaking study, published in eClinicalMedicine and led by researchers affiliated with the University of Heidelberg, has shed light on the secondary cancer risks associated with CAR-T cell therapy. The study, funded by grants from the Natural Science Foundation of Guangdong Province and several national Chinese scientific foundations, analysed 607 reported cases of secondary malignancies occurring from 2017 through 2023 using global pharmacovigilance databases.
The study underscores secondary primary malignancies as a tangible risk factor in CAR-T therapy. Pediatric and young adult patients under the age of 40 are particularly vulnerable to secondary cancers following CAR-T administration. These patients experienced secondary cancers within a median timeframe of 35 days post-treatment, significantly earlier than in matched controls, with a median onset of 282 days post-therapy.
The significantly heightened risks of T-cell lymphoma and myelodysplastic syndromes are a pivotal concern. The accelerated onset of secondary cancers post-treatment is a critical safety dimension of CAR-T therapy. The research team declared no financial or personal affiliations that could bias results.
The findings raise several mechanistic research questions about the impact of CAR-T cells on host genomic stability and pro-oncogenic inflammation within the bone marrow niche. Interactions between CAR-T therapy and patients' prior treatment histories require further investigation.
The authors of the study advocate for the systematic inclusion of SPM risk assessments in future CAR-T clinical trial designs and post-market surveillance programs. They also endorse the recent United States Food and Drug Administration (FDA) directive mandating lifelong monitoring of CAR-T recipients.
The authors emphasize the importance of comprehensive pharmacovigilance for optimizing risk-benefit profiles of CAR-T treatments. Multidisciplinary collaboration between clinicians, biologists, and regulatory agencies will be essential in balancing transformative therapeutic benefits with long-term health risks in CAR-T cell therapy.
The insights gained from this study will be instrumental in shaping safer treatment paradigms for CAR-T cell therapy. The authors advocate for the integration of routine screening programs customized by patient age and risk profile to detect SPMs early. The study's findings highlight the need for vigilance when adopting novel biotechnologies like CAR-T therapy at scale.
