Low Secondary Cancer Risk Post CAR T Cell Treatment: Stanford Study

Despite the FDA's warnings regarding CAR-T cell therapies, a comprehensive study led by Stanford Medicine has revealed that the risk of secondary malignancies associated with these treatments is relatively low. The findings, published in The New England Journal of Medicine, stem from an analysis of 724 patients who received CAR-T therapies at Stanford Health Care between 2016 and 2024. The study indicated that about 6.5% of these patients developed secondary cancers over a median follow-up period of three years.

According to Stanford's announcement, this occurrence rate is “roughly similar” to patients treated with stem cell therapy. The study found one instance where a patient succumbed to a secondary T-cell cancer, which researchers believe was likely due to the immunosuppression linked with CAR-T therapies rather than an error in the gene insertion process during treatment preparation.

Detailed examinations of both the primary and secondary cancers revealed distinct immunophenotypes and genomic profiles, leading researchers to suggest that the CAR-T therapy itself was not the cause of the secondary malignancies. David Miklos, co-senior author of the study and chief of bone marrow transplantation and cell therapy at Stanford, emphasized the importance of understanding how immunosuppression exacerbates cancer risk following CAR-T treatment. This knowledge becomes particularly crucial as the CAR-T field expands its focus from high-risk, refractory blood cancers to lower-risk yet significant disorders, including autoimmune diseases.

Stanford's findings are consistent with research from Penn Medicine published in Nature Medicine in January 2024. Although the Penn study involved a smaller sample size of 449 patients, the results were comparable. Over a median follow-up of 10.3 months, only 16 patients developed secondary cancers, predominantly solid tumors such as skin and prostate cancer. There was just one case of secondary T-cell lymphoma, which exhibited very low levels of the CAR transgene.

These studies from Stanford and Penn offer a measure of reassurance regarding the safety of CAR-T therapies. In November 2023, the FDA began investigating this class of drugs following reports of secondary malignancies in patients who had received approved CAR-T products. Consequently, in April 2024, the FDA mandated a class-wide black box warning to highlight the associated risks.

The six commercially available CAR-T therapies affected by this warning include Gilead’s Tecartus (brexucabtagene autoleucel) and Yescarta (axicabtagene ciloleucel), Bristol Myers Squibb’s Abecma (idecabtagene vicleucel) and Breyanzi (lisocabtagene maraleucel), Novartis’ Kymriah (tisagenlecleucel), and Johnson & Johnson’s Carvykti (ciltacabtagene autoleucel).

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