CD7 CART Therapy Bridging Allo-HSCT Remarkably Improves Long-Term DFS in Refractory/Relapsed T-ALL/LBL.

Abstract

T-ALL is caused by abnormal proliferation of T cells. It comprises 25%-50% of ALL cases in children and adults. Outlook for R/R T-ALL/LBL and patients over 60 even dimmer. The treatment is challenging due to its biological and genetic diversity, limiting the development of effective targeted and immunotherapeutic strategies. Salvaged allo-HSCT offers only 20%-30% DFS. This current study retrospectively analyzed 90 patients with R/R T-ALL (40, 44.4%) or T-LBL (50, 55.6%) treated at Beijing Gobroad Boren Hospital from February 2018 to January 2023. The median age was 14 (range: 2-65) years old. Somatic and germline gene mutations were detected by sequencing pre-transplant. Thirty-two (35.6%) patients were sensitive to chemotherapy and achieved CR before transplant (CR group), and 58 (64.4%) cases were resistant to chemotherapy and in non-remission (NR) pre-HSCT. Forty-one of 58 patients in NR received CD7 CAR-T before allo-HSCT (CART group) and the rest 17 patients in NR underwent salvaged transplant (NR group). The results indicate that CD7 CAR-T group have OS (p=0.029; 2-year OS rates: 54.4% (95% CI: 38.9-76.0%)) and DFS (p=0.00032; 2-year DFS: 51.0% (95% CI: 36.9-70.7%)) similar to those in the CR group, but better than those in the NR group. The CIR for CD7 CAR-T group and CR group was significantly lower than NR group after one year (p=0.0016; CAR-T group 2-year CIR: 31.67% (95% CI: 19.3-49.2%)). Our study examined the somatic and germline gene mutations in R/R T-ALL/LBL and evaluated the prognosis after transplantation. Based our limited study, we found that using CD7 CAR T cells followed by allo-HSCT greatly enhanced the long-term DFS of chemo resistant T-ALL/LBL patients.