Anti-CD19 CAR T-cell consolidation therapy combined with CD19+feeding T cells and TKI for Ph plus acute lymphoblastic leukemia

作者：Chen, Li-Yun; Gong, Wen-Jie; Li, Ming-Hao; Zhou, Hai-Xia; Xu, Ming-Zhu; Qian, Chong-Sheng; Kang, Li-Qing; Xu, Nan; Yu, Zhou; Qiao, Man; Zhang, Tong-Tong; Zhang, Ling; Tian, Zheng-Long; Sun, Ai-Ning; Yu, Lei; Wu, De-Pei; Xue, Sheng-Li^*

来源：Blood Advances, 2023, 7(17): 4913-4925.

DOI：10.1182/bloodadvances.2022009072

• TERM-FOLLOW-UP
• TYROSINE KINASE INHIBITORS
• YOUNG-ADULTS
• HYPER-CVAD
• CHEMOTHERAPY
• DASATINIB
• IMATINIB
• MANAGEMENT
• LYMPHOMA
• KINETICS

We conducted a single-arm, open-label, single-center phase 1 study to assess the safety and efficacy of multicycle-sequential anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in combination with autologous CD19+ feeding T cells (FTCs) and tyrosine kinase inhibitor (TKI) as consolidation therapy in patients under the age of 65 years with de novo Ph-positive CD19+ B-cell acute lymphoblastic leukemia. Participants were given induction chemotherapy as well as systemic chemotherapy with TKI. Afterward, they received a single cycle of CD19 CAR T-cell infusion and another 3 cycles of CD19 CAR T-cell and CD19+ FTC infusions, followed by TKI as consolidation therapy. CD19+ FTCs were given at 3 different doses. The phase 1 results of the first 15 patients, including 2 withdrawals, are presented. The most common adverse events were cytopenia (13/13) and hypogammaglobinemia (12/13). There was no incidence of cytokine release syndrome above grade 2 or immune effector cell-associated neurotoxicity syndrome or grade 4 nonhematological toxicities. All 13 patients achieved complete remission, including 12 patients with a complete molecular response (CMR) at the data cutoff. The relapse-free survival was 84%, and the overall survival was 83% with a median follow-up of 27 months. The total number of CD19-expressing cells decreased with an increasing CMR rate. CD19 CAR T cells survived for up to 40 months, whereas CD19+ FTCs vanished in 8 patients 3 months after the last infusion. These findings could form the basis for the development of an allo-HSCT-free consolidation paradigm. This trial was registered at www.clinicaltrials. gov as #NCT03984968.

• 单位
  苏州大学; 1