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Comparing the efficacy of salvage regimens for relapsed/refractory B-cell acute lymphoblastic leukaemia: a systematic review and network meta-analysis

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Abstract

The complete remission (CR) rate and overall survival (OS) of relapsed/refractory (R/R) B-cell acute lymphoblastic leukaemia (B-ALL) are not satisfactory. The available salvage regimens include standard chemotherapy, inotuzumab ozogamicin, blinatumomab and cluster of differentiation (CD)19 chimeric antigen receptor T cells (CAR T), and the NCCN guidelines recommend all of these therapies with no preference. Dual CD19/CD22 CAR T-cells have emerged as new treatments and have shown some efficacy, with high CR rates and preventing CD19-negative relapse. However, direct comparisons of the CR rate and long-term survival among the different salvage therapies are lacking. Databases including PubMed, Embase, Web of Science and Cochrane were searched from inception to January 31, 2022, for relevant studies. The outcomes of interest were complete remission/complete remission with incomplete haematologic recovery (CR/CRi) rates and 1-year overall survival (OS) rates. Odds ratios (ORs) were generated for binary outcomes, and the mean difference (MD) was generated for consecutive outcomes by network meta-analysis. CD19 CAR T-cells demonstrated a significantly better effect in improving the CR/CRi rate than blinatumomab (OR = 8.32, 95% CI: 1.18 to 58.44) and chemotherapy (OR = 16.4, 95% CI: 2.76 to 97.45). In terms of OS, CD19 CAR T-cells and dual CD19/CD22 CAR T-cells both had a higher 1-year OS rate than blinatumomab, inotuzumab ozogamicin and chemotherapy. There was no significant difference between CD19 CAR T-cells and dual CD19/CD22 CAR T-cells in terms of 1-year OS and CR/CRi rates. CD19 CAR T-cells are effective in inducing CR, and CD19 CAR T-cells and dual CD19/CD22 CAR T-cells show benefits for overall survival. More high-quality randomized controlled trials and longer follow-ups are needed to confirm and update the results of this analysis in the future.

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Funding

This work was supported by the grants from the National Natural Science Foundation of China (Grant No. 81970138, 82270165), Jiangsu Province Natural Science Foundation of China (Grant No. 20221235). Translational Research Grant of NCRCH (Grant No. 2020ZKMB05), Jiangsu Province ‘333’ Project, Social Development Project of the Science and Technology Department of Jiangsu (Grant No. BE2021649) and Gusu Key Medical Talent Program (Grant No. GSWS2019007), Jiangsu Province Natural Science Foundation of China (Grant No. BK20221235).

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Han-Yu Cao was responsible for protocol writing, data analysis and manuscript writing. Chao-Ling Wan was responsible for data extraction. Sheng-Li Xue helped perform the analysis with constructive discussions.

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Correspondence to Sheng-Li Xue.

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Cao, HY., Wan, CL. & Xue, SL. Comparing the efficacy of salvage regimens for relapsed/refractory B-cell acute lymphoblastic leukaemia: a systematic review and network meta-analysis. Ann Hematol 102, 155–165 (2023). https://doi.org/10.1007/s00277-022-05040-1

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