Chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed, refractory CLL: a systematic review and meta-analysis.

OBJECTIVES

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by the excessive production of lymphocytes in the bone marrow. One of the emerging therapeutic strategies for CLL is chimeric antigen receptor (CAR) T-cell therapy, wherein T-cells are genetically modified to recognize and target cancer cells more effectively. The present study aims to systematically compare the therapeutic impact of high-dose versus low-dose status of CAR T-cell therapy targeting CD19 (CART-19) in patients with relapsed or refractory CLL.

METHODS

To identify relevant studies, a comprehensive literature search was conducted in PubMed, Scopus, and Web of Science databases up to April 2023. The primary outcome measures included treatment response rates, assessed as complete response (CR) and partial response (PR), and toxicity, as indicated by the incidence of cytokine release syndrome (CRS). Additionally, sensitivity and bias analyses were performed to evaluate the robustness of the findings.

RESULTS

Four randomized controlled trials (RCTs) comprising 89 patients with relapsed or refractory CLL met the inclusion criteria. Comparison of treatment response rates between high-dose and low-dose CART-19 therapy demonstrated a significantly higher complete and partial response rate in the high-dose group (SMD [95% CI]: 1.02 [0.10, 1.94]; P<0.05). However, no significant association was observed between CTL019 dosage and the incidence of CRS (P>0.05).

CONCLUSION

This meta-analysis suggests that high-dose CART-19 is associated with improved response rates and survival outcomes in patients with CLL compared to low-dose therapy. However, due to variability in study results, further large-scale, well-designed trials are required to establish the optimal therapeutic dosing strategy for CART-19 therapy in CLL.