A recent study from Memorial Sloan Kettering Cancer Center (MSKC) indicates that CAR-T therapy does not increase the risk of secondary cancers in patients treated for lymphoma or multiple myeloma. This finding contradicts current warning labels on CAR-T therapies and suggests a need for revision. The research, presented in Clinical Cancer Research, analyzed data from multiple clinical trials and real-world studies, involving over 5,500 patients.
Study Details and Findings
The study, led by Dr. Kai Rejeski, reviewed data from 18 clinical trials and seven real-world studies. The analysis included patients who received one of the six FDA-approved CAR-T cell therapies: idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta). Over a median follow-up of nearly 22 months, 326 secondary cancers developed, representing 5.8% of the patient population.
Notably, when comparing patients who received CAR-T therapy to those on standard regimens, the rates of secondary cancers were similar: 5% in the CAR-T group versus 4.9% in the non-CAR-T group. The risk did not significantly change based on the type of cancer being treated or the specific CAR-T therapy used. However, patients who underwent more than three courses of non-CAR-T treatments prior to CAR-T therapy showed a higher risk of secondary cancers.
Implications for Clinical Practice
The U.S. Food and Drug Administration (FDA) issued a boxed warning on CAR-T therapies in January, cautioning about the potential increased risk of secondary T-cell cancers. This warning was based on data from the FDA's Adverse Event Reporting System. However, Dr. Rejeski and his team argue that this data may not account for other risk factors such as patient age, prior treatments, and follow-up duration.
"I worry that the warning labels may intimidate patients who receive this therapy, which may not be entirely founded," Dr. Rejeski stated in a news release from the American Association for Cancer Research. He emphasized the importance of interpreting the data cautiously and contextualizing it for patients.
T-Cell Malignancies
Further analysis revealed that only a small fraction of the secondary cancers were T-cell malignancies (0.09%). Among these, only one case showed a genetic relation to the T-cells used in the CAR-T therapy. This suggests that the risk of CAR-T therapy directly causing secondary T-cell cancers is minimal.
CAR-T Therapy Benefits
Dr. Rejeski also pointed out that CAR-T therapy has significantly improved survival rates for patients with refractory large B-cell lymphoma. "CAR-T therapy is the first treatment in more than 20 years to show an overall survival benefit compared to the standard of care in refractory large B-cell lymphoma," he said. He advises against withholding this therapy due to the minimal risk of developing T-cell malignancies.
