Jinglei Yu, Fengmei Song, Mingming Zhang, Mingfeng Zhao, Wei Sang, Songfu Jiang, Lixin Wang, Xingbing Wang, Sanfang Tu, Yuhua Li, He Huang, Yongxian Hu, Guoqing Wei
BACKGROUND: Although chemotherapy-free regimens have improved initial remission rates in patients with newly diagnosed Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph + B-ALL), outcomes for relapsed or refractory (R/R) Ph + B-ALL remain poor. This study reports the efficacy and safety of CD19 chimeric antigen receptor (CAR) T-cell therapy in R/R Ph + B-ALL. METHODS: This study retrospectively analyzed 93 patients with R/R Ph + B-ALL who received CD19 CAR T-cell therapy across China between August 2015 and March 2024. We evaluated the overall response rates, long-term efficacy, safety, and prognostic factors associated with CD19 CAR T-cell therapy. RESULTS: Complete remission (CR) or CR with incomplete hematologic recovery rate was 87.1% (81/93), with 96.3% (78/81) of responders achieving minimal residual disease negativity by flow cytometry. Molecular response rate was 78.5% (73/93), including 63.4% achieving complete molecular remission and 15.1% major molecular remission. Twenty patients underwent consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT). After a median follow-up of 25.4 months (range, 0.1-68.5), the median overall survival (OS) was 20.8 months, and the median leukemia-free survival (LFS) was 8.1 months. Better Eastern Cooperative Oncology Group performance status and absence of adverse genetic features were associated with improved OS and LFS. In contrast, consolidative allo-HSCT following CAR T-cell therapy was not independently associated with improved OS or LFS. Grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 14.0% and 2.2% of patients, respectively. The most common and predictable adverse events were hematologic, primarily cytopenias, which were manageable with supportive care. CONCLUSIONS: CD19 CAR T-cell therapy can achieve high response rates and long-term clinical benefits for patients with R/R Ph + B-ALL, with a manageable safety profile. STATEMENT OF PRIOR PRESENTATION: The preliminary study was presented as a poster presentation (Publication Number: 4201) at the 66th American Society of Hematology Annual Meeting, San Diego, CA, on December 7-10, 2024.