Study Reveals Increased Secondary Cancer Risks After CAR-T Treatment

CAR-T cell therapy has achieved remarkable success in treating blood cancers that were once considered incurable, helping thousands of patients each year. Despite these positive outcomes, concerns have been growing about the risk of secondary primary malignancies (SPMs) related to CAR-T therapy. To address these worries, a team from Southern Medical University in China undertook an extensive study, as described in eClinicalMedicine, to investigate secondary cancer risks associated with CAR-T treatments using the largest existing dataset.

Peng Luo, corresponding author of the study, highlights the importance of this research. “CAR-T therapy has transformed the treatment landscape for refractory blood cancers, but we need to understand the full safety profile to optimize patient care.” The team analyzed 607 cases from global pharmacovigilance databases spanning from 2017 to 2023, making this the most detailed examination of SPMs after CAR-T therapy currently available. 

The study’s findings indicate that patients treated with CAR-T therapy have a notably higher likelihood of developing certain secondary cancers. Specifically, there was an 8.9-fold increased risk for T-cell lymphoma and a 3.5-fold increased risk for myelodysplastic syndromes compared to those not undergoing CAR-T treatment. The timing of these secondary cancers was also significant: the median onset for SPMs following CAR-T was 282 days, considerably earlier than the 526-day median seen in other patients. Moreover, younger patients—those under age 40—were shown to develop secondary cancers much more rapidly, with a median onset of just 35 days after CAR-T therapy.

According to Jian Zhang, the study’s senior author, “Until now, our knowledge of secondary primary malignancies following CAR-T therapy was limited to small case reports and retrospective studies. Our approach using global pharmacovigilance databases shows that comprehensive safety monitoring is essential for all CAR-T recipients.” Dr. Zhang emphasizes the importance of their work in supporting “the FDA’s recent mandate for lifelong monitoring of all CAR-T patients” and suggests that clinicians should adopt tailored cancer screening protocols for different age groups based on their findings.