CD19 CAR-T cell treatment conferred sustained remission in B-ALL patients with minimal residual disease

• Published in: Cancer Immunology, Immunotherapy Vol. 70; no. 12; pp. 3501 - 3511
• Main Authors: Lu, Wenyi, Wei, Yunxiong, Cao, Yaqing, Xiao, Xia, Li, Qing, Lyu, Hairong, Jiang, Yili, Zhang, Huan, Li, Xin, Jiang, Yanyu, Meng, Juanxia, Yuan, Ting, Zhu, Haibo, He, Xiaoyuan, Jin, Xin, Sun, Rui, Sui, Tao, Liu, Kaiqi, Zhao, Mingfeng
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2021; Springer Nature B.V
• Subjects: Acute lymphoblastic leukemia; Adolescent; Adult; Aged; Antigens, CD19 - immunology; Cancer Research; CD19 antigen; Chemotherapy; Chimeric antigen receptors; Clinical trials; Cytokines; Female; Humans; Immunology; Immunotherapy, Adoptive - methods; Lymphatic leukemia; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma, B-Cell - immunology; Male; Medicine; Medicine & Public Health; Middle Aged; Minimal residual disease; Neoplasm, Residual - immunology; Oncology; Original; Original Article; Patients; Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology; Progression-Free Survival; Receptors, Chimeric Antigen - immunology; Recurrence; Remission; Remission (Medicine); T-Lymphocytes - immunology; Young Adult; CD19-directed chimeric antigen receptor T cells; Minimal residual disease; Cytokine release syndrome; Relapse; B-cell acute lymphoblastic leukemia
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-021-02941-4

The persistence or recurrence of minimal residual disease (MRD) after chemotherapy predicts relapse of B-cell acute lymphoblastic leukemia (B-ALL). CD19-directed chimeric antigen receptor T (CD19 CAR-T) cells have shown promising responses in B-ALL. However, their role in chemotherapy-refractory MRD-positive B-ALL remains unclear. Here we aimed to assess the effectiveness and safety of CD19 CAR-T cells in MRD-positive B-ALL patients. From January 2018, a total of 14 MRD-positive B-ALL patients received one or more infusions of autogenous CD19 CAR-T cells. Among them, 12 patients achieved MRD-negative remission after one cycle of CAR-T infusion. At a median follow-up time of 647 days (range 172–945 days), the 2-year event-free survival rate in MRD-positive patients was 61.2% ± 14.0% and the 2-year overall survival was 78.6 ± 11.0%, which were significantly higher than patients with active disease (blasts ≥ 5% or with extramedullary disease). Moreover, patients with MRD had a lower grade of cytokine release syndrome (CRS) than patients with active disease. However, the peak expansion of CAR-T cells in MRD positive patients showed no statistical difference compared to patients with active disease. Five patients received two or more CAR-T cell infusions and these patients showed a decreased peak expansion of CAR-T cell in subsequent infusions. In conclusion, pre-emptive CD19 CAR-T cell treatment is an effective and safe approach and may confer sustained remission in B-ALL patients with chemotherapy-refractory MRD. The trials were registered at www.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018).