Genomic correlates of clinical CAR T cell activity

Researchers analyzed whole germline sequencing from patients with lymphoma in the ZUMA-1 and ZUMA-7 clinical trials who were treated with axicabtagene ciloleucel CAR T-cell products in order to identify germline variants influencing clinical toxicity. They found that in the ZUMA-1 cohort, STXBP2 variants correlated with more severe toxicity, whereas in both trials, ADAMTSL3 correlated with protection from toxicity. Additionally, PTPN22 was strongly associated with enhanced CAR T-cell expansion.