CAR-T cell therapy linked to increased risk of secondary primary malignancies globally

Each year, thousands of patients worldwide receive CAR-T cell therapy for blood cancers, achieving remarkable success in treating previously incurable conditions. However, concerns about secondary primary malignancies (SPMs) following this revolutionary treatment have prompted global regulatory attention. In a study published in eClinicalMedicine, a group of researchers from China examined the largest dataset to date analyzing secondary cancer risks after CAR-T therapy.

"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," explains Dr. Peng Luo, corresponding author from the Department of Oncology at Zhujiang Hospital, Southern Medical University. "Our analysis of global pharmacovigilance databases represents the most comprehensive examination of secondary primary malignancies following CAR-T therapy, covering 607 cases from 2017 to 2023."

The study's multidisciplinary team of scientists found that patients receiving CAR-T therapy showed significantly increased risks of developing secondary cancers, particularly T-cell lymphoma and myelodysplastic syndromes. The research revealed an 8.9-fold increased risk for T-cell lymphoma and a 3.5-fold increased risk for myelodysplastic syndromes compared to patients not receiving CAR-T therapy. Most concerning was the timing: secondary cancers occurred much earlier in CAR-T recipients, with a median onset of 282 days compared to 526 days in other patients. The researchers also discovered age-specific patterns, with pediatric and young adult patients under 40 experiencing secondary cancers within just 35 days of treatment.

According to Dr. Jian Zhang, senior author of the study, this represents a crucial advancement in understanding CAR-T therapy safety. "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." He adds: "We hope that our results encourage clinicians to implement customized screening protocols for different age groups and support the FDA's recent mandate for lifelong monitoring of all CAR-T patients."