Efficacy and Safety of Blinatumomab for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Systemic Review and Meta-Analysis

Abstract

Objective: The aim was to evaluate the efficacy and safety of blinatumomab monotherapy for the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL).

Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched to collect clinical studies related to blinatumomab. The primary outcome measures were complete remission (CR), and minimal residual disease (MRD) response. Prognostic indicators included overall survival (OS) and relapse-free survival time (RFS). Grade ≥3 adverse reactions were mainly analyzed for safety, including cytokine release syndrome (CRS), neurological events and hematological toxicity. The heterogeneity was quantified by I² statistic, which reflected the proportion of the true heterogeneity to the variance of the total effect size. Studies were considered heterogeneous if the I² statistic was greater than 50%, and conversely, studies were homogeneous.

Results: A total of 18 studies involving 1,373 patients were included. The analysis results showed a CR rate of 54% (95%CI:44%-64%) and an MRD response rate of 43% (95%CI:34%-51%). The CR rate was higher in patients with bone marrow (BM) blast <50% than in patients with BM blast ≥50% (71% vs. 34%). The median OS and RFS were 8.16 months (95%CI:6.64-9.69) and 6.02 months (95%CI:4.63-7.41), respectively. For safety analysis, the incidence of grade ≥3 adverse events (AEs) was 80% (95%CI:72%-88%), the incidence of grade ≥3 neurological toxicity was 7% (95%CI:4%-11%), and the incidence of grade ≥3 CRS was 3% (95%CI:2%-5%). However, the mixture of retrospective and prospective studies led to heterogeneity to some extent in this meta-analysis.

Conclusion: Blinatumomab is effective in the treatment of R/R B-ALL with a controlled occurrence of AEs and a reliable safety profile.

Keywords: Adverse event; Bispecific antibody; CD19; Complete remission; Outcome.