Differences in efficacy and safety among CAR-Ts anti-CD19/CD22, anti-CD19, and anti-CD22, in adult patients with relapse/refractory B-cell acute lymphoblastic leukemia: a meta-analysis and systematic review

Abstract

Relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) is a challenging disease with low rates of remission and survival in adult patients. Anti-CD19 Chimeric Antigen Receptor T-cells (CAR-Ts) therapies have been approved for these patients. Dual-target CAR-Ts against CD19 and CD22 have recently been developed to improve the efficacy of the single-target therapy; however, extent of the improvement using this dual-target therapy has yet to be determined. We performed a meta-analysis of the outcome and safety of CAR-Ts, comparing anti-CD19 vs anti-CD22 vs dual-target anti-CD19/CD22 CAR-Ts, to elucidate the differences and limitations of these therapies in adult patients with R/R B-ALL. Although the limitations of our study derived from heterogeneity in the included publications, our results suggest that anti-CD19/CD22 CAR-Ts generate lower incidence of relapse and neurotoxicity, but similar results were obtained regarding complete remission, minimal residual disease, overall survival, and cytokine release syndrome compared with single-target anti-CD19 and anti-CD22 CAR-Ts.

Keywords:

• Chimeric antigen receptors
• leukemia
• dual-targeting
• bispecific CAR

Author contributions

JB-R designed the study; EO-S supervised the research; YAD-M and JB-R collected the information; JB-R, EO-S, and YAD-M wrote the manuscript; JB-R performed the statistical analysis. All the authors read and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

JB-R received a scholarship from Consejo Nacional de Humaninades, Ciencia y Tecnología (CVU 1146686). This funding agency did not participate in the design, performance, analysis, nor writing of this research.