Secondary Cancer Risk Is Low After CAR T Cell Treatment: Stanford Study

2024-06-13

免疫疗法细胞疗法临床结果

Pictured: 3D illustration of a CAR-T cell attacking a cancer cell/iStock, Meletios Verras Despite warnings about the drug class from the FDA, a large study led by Stanford Medicine has found that CAR-T cell therapies carry only a low risk of secondary malignancies. The results, published Wednesday in The New England Journal of Medicine, come from a review of 724 patients who had undergone CAR-T therapies at Stanford Health Care between 2016 and 2024. Overall, the study found that secondary cancers arose in approximately 6.5% of patients over a median follow-up period of three years. According to Stanford’s announcement on Wednesday, this incidence rate was “roughly similar” to patients who had been treated instead with stem cell therapy. The study identified one patient who died due to a secondary T-cell cancer, though Stanford researchers contend this was likely caused by the immunosuppression associated with CAR-T therapies, rather than a mis-insertion of the gene for the CAR construct during the preparation of the treatment. Deep profiling of both the original and secondary cancers found that they had “distinct immunophenotypes and genomic pro ” according to researchers, suggesting that that the CAR-T therapy was not responsible for the secondary malignancy. “These results may help researchers focus on the immune suppression that can precede and often follows CAR-T therapy,” David Miklos, co-senior author of the study and chief of bone marrow transplantation and cell therapy at Stanford, said in a statement. Understanding how immunosuppression aggravates cancer risk after CAR-T treatment is especially important “as the CAR-T cell field pivots from treating high-risk, refractory blood cancers to lower risk, but clinically important, disorders including autoimmune diseases,” Miklos said. Stanford’s findings echo that of Penn Medicine, which in January 2024 published a paper in Nature Medicine that also found a low risk of secondary cancers after CAR-T treatment. The Penn researchers used a smaller sample size—449 patients—but their figures were similar: Over a median follow-up of 10.3 months, only 16 patients developed secondary cancers, most of which were solid tumors such as skin and prostate cancer. There was only one case of secondary T-cell lymphoma, which showed only “very low” levels of the CAR transgene. The respective findings from Stanford and Penn could help allay some concerns about the safety of CAR-T therapies. In November 2023, the FDA announced that it was investigating the drug class after it identified cases of secondary malignancies in patients who had received approved CAR-T products. The probe pushed the regulator in April 2024 to require a class-wide black box warning flagging the risk. All six commercially available CAR-T therapies were impacted including 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). Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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