T-cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous hematological malignancy that accounts for 25% to 50% of all cases in both children and adults. The genetic diversity of T-ALL itself limits the development of targeted therapy and immunotherapy in this field to some extent, so the clinical treatment of T-ALL is faced with many difficulties, and the prognosis of patients with relapsed/refractory T-cell acute lymphoblastic leukemia/T-cell lymphoblastic lymphoma (R/R T-ALL/LBL) is even less ideal.

Recently, the team led by Director Zhihui Li in Director Tong Wu’s team at Beijing GoBroad Boren Hospital has published a paper in the journal Transplantation and Cellular Therapy which, focusing on the dilemma of diagnosis and treatment of R/R T-ALL/LBL, investigated the long-term outcomes in R/R T-ALL/LBL patients treated with CD7 CAR-T bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT) at Beijing Boren Hospital, and demonstrated that this combination strategy could improve long-term disease-free survival (DFS) in this patient population.

Compared with B-cell blood tumors, the CAR-T therapy of T-cell blood tumors is quite challenging. Previously, the teams of Director Tong Wu and Director Zhihui Li explored CD7 CAR-T bridging allo-HSCT in the treatment of T-cell blood tumors and their research results have been presented on many international academic occasions such as the American Society of Hematology (ASH) Annual Meeting and the European Hematology Association (EHA) Annual Meeting. They have shared the valuable experience of the Boren’s physician teams in the field of CAR-T for T-cell blood tumors with global peers for consecutive years.

Study Abstract

The study retrospectively analyzed 90 patients with R/R T-ALL (n=40) or T-LBL (n=50) treated at Beijing GoBroad Boren Hospital from February 2018 to January 2023. The median age was 14 (range: 2-65) years old.

All patients had received chemotherapy prior to transplantation, and the median number of lines of pre-transplantation treatment was 4 (range: 1-7). 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 (CAR-T group) and the rest 17 patients in NR underwent salvaged transplant (NR group).

After a median follow-up of 25.5 (95% CI: 19.6-32) months, the overall survival (OS) and DFS in the CAR-T group were similar to those in the CR group and superior to those in the NR group. The 2-year OS was 54.4%, 69.9%, and 35.3%, and the 2-year DFS was 51.0%, 61.1%, and 17.6%, respectively. After 1 year, the cumulative recurrence rate in the CAR-T and CR groups was significantly lower than that in the NR group (31.67% and 29.0% vs. 70.5%). In addition, the treatment-related mortality was 17.29%, 9.8%, and 11.76%, respectively (p=0.65).

Prior to transplantation, somatic and germline gene mutations in T-ALL/LBL patients were detected by NGS in this study, and the results showed that TP53 and MED12 mutations were significantly associated with high recurrence and mortality after transplantation.

However, multivariate analysis showed that MED12 mutation did not affect OS (p=0.49) or DFS (p=0.394).

Study Conclusion

This retrospective study demonstrated that CD7 CAR-T bridging allo-HSCT significantly improved long-term DFS in patients with chemotherapy-resistant T-ALL/LBL, and achieved safety and efficacy comparable to those in the CR group. CD7 CAR-T (p=0.037), TBI conditioning (p=0.002), and cGVHD (p=0.004) were independent protective factors for OS, while aGVHD (p=0.034) and TP53 mutation (p=0.002) were independent risk factors for OS. CD7 CAR-T (p=0.005) and TBI conditioning (p=0.024) were protective factors for DFS, while TP53 mutation (p=0.02) was a risk factor for DFS. At the same time, the study also revealed the overview of somatic and germline gene mutations in R/R T-ALL/LBL patients, and preliminarily identified the gene mutation factors affecting the transplant outcome.