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

• Published in: Blood advances 2023-09, Vol.7 (17), p.4913-4925
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Clinical Trials and Observations
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2022009072

•CD19 CAR T-cell consolidation therapy combined with CD19+ FTCs and TKI had a manageable long-term safety profile.•CD19 CAR T-cell consolidation therapy combined with CD19+ FTCs and TKI yielded a high response rate and duration. [Display omitted] 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 who are not eligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). 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 the following 3 different doses: 2 × 106/kg, 3.25 × 106/kg, and 5 × 106/kg. The phase 1 results of the first 15 patients, including 2 withdrawals, are presented. Phase 2 research is still ongoing. 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 on 31 March 2022. The relapse-free survival was 84%, and the overall survival was 83% with a median follow-up of 27 months (7-57 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 merit further evaluation and could form the basis for the development of an allo-HSCT–free consolidation paradigm. This trial was registered at www.clinicaltrials.gov as #NCT03984968.