Anti-CD19 CAR-T cell therapy bridge to HSCT decreases the relapse rate and improves the long-term survival of R/R B-ALL patients: a systematic review and meta-analysis

Abstract

Chimeric antigen receptor (CAR) T cell therapy improves the remission rate of refractory/relapsed B-acute lymphoblastic leukemia (R/R B-ALL) patients, but the relapse rate remains high. Recent studies suggest patients who underwent post-chimeric antigen receptor T cell therapy hematopoietic stem cell transplantation (post- HSCT) would achieve durable remission and better survival, but this remains controversial. To this end, we conducted a meta-analysis to assess the role of post-HSCT in R/R B-ALL. The Cochrane Library, Embase, and PubMed were used to identify relevant studies; the latest search update was on July 05, 2020. We used the Cochran Q test and I-squared statistics to test for heterogeneity among the studies analyzed. The fixed model and random model were used to combine results when appropriate. We performed all statistical analyses with Stata 12, and P < 0.05 was considered statistically significant. We included 18 studies with 758 patients in the meta-analysis. Our results indicated that post-HSCT was associated with lower relapse rate (RR: 0.40, 95% CI: 0.32–0.50, P = 0.000), better overall survival (HR: 0.37, 95% CI: 0.19–0.71, P = 0.003), better leukemia-free survival (HR: 0.20, 95% CI: 0.10–0.40, P = 0.000). However, post-HSCT did not influence OS in Caucasians, and CAR-T cells with CD28 co-stimulation factor bridged to HSCT did not influence OS. Post-HSCT decreased the relapse rate and improved the long-term survival of R/R B-ALL patients. R/R B-ALL patients would benefit from post-HSCT after CAR-T cell therapy.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

BM:

Bone marrow

CAR-T cell:

Chimeric antigen receptor T cell

CR:

Complete remission

CI:

Confidence interval

EFS:

Event-free survival

HR:

Hazard ratio

HSCT:

Hematopoietic stem cell transplantation

LFS:

Leukemia-free survival

MRD:

Minimal residual disease

NOS:

Newcastle-Ottawa Quality Assessment Scale

OS:

Overall survival

RR:

Relative risk

post-HSCT:

Post-chimeric antigen receptor T cell therapy hematopoietic stem cell transplantation

R/R B-ALL:

Refractory/relapsed B-acute lymphoblastic leukemia

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Funding

This work was supported by the National Natural Science Foundation of China: [grant number 81670179]; Major Subject of Science and Technology of Anhui Province: [grant number 201903a07020030]; Key Research and Development Plan of Anhui Province, China (201904a07020058); and the Foundation of Anhui Medical University (2019xkj134).

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LHH and AC performed data collection; LHH analyzed the data and wrote the manuscript; AC, QL, WWZ, and QST, wrote the manuscript,; SDX and ZMZ wrote the manuscript and approved the final manuscript as submitted.

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Correspondence to Shudao Xiong or Zhimin Zhai.

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Hu, L., Charwudzi, A., Li, Q. et al. Anti-CD19 CAR-T cell therapy bridge to HSCT decreases the relapse rate and improves the long-term survival of R/R B-ALL patients: a systematic review and meta-analysis. Ann Hematol (2021). https://doi.org/10.1007/s00277-021-04451-w

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Keywords

  • CAR-T cell therapy
  • Hematopoietic stem cell transplantation
  • R/R ALL
  • Survival
  • Relapse
  • Meta-analysis