Anti‐CD19 chimeric antigen receptor‐modified T cells for B‐cell malignancies: a systematic review of efficacy and safety in clinical trials

OBJECTIVES: Administration of anti-CD19 chimeric antigen receptor (CAR)-modified T cells for B-cell malignancies has been remarkably effective in recent clinical trials. To investigate the critical parameters affecting efficacy and evaluated the safety of using CAR T cells targeting CD19 in B-lineage malignancies. We performed a systematic review of reported phase I clinical trials using CAR T cells targeting CD19 in B-lineage malignancies. METHODS: We searched Medline and Embase for studies on anti-CD19 CAR-modified T cells in patients with B-cell malignancies in October 2014. Univariate analyses were performed using the Kaplan-Meier method, and a Cox regression model was used to determine the independent prognostic factors of progression-free survival (PFS). RESULTS: Six trials involving 50 patients were included in this review. After CAR T-cell infusion, the overall response rate was 48% (complete responses in 24%). The 6-month PFS and 1-year PFS were 43% and 27%, respectively. Statistically significant factors favorably influencing PFS were conditioning chemotherapy (P < 0.001), B-cell aplasia (P = 0.040), and durable persistence of CAR T cells (P = 0.013) in univariate analyses. After multivariate analysis, conditioning chemotherapy remained as an independent prognostic factor for PFS. The most common adverse events were fever, hypotension, rigor, fatigue, bacteremia, chill, dyspnea, and headache, but all were temporary and resolved. CONCLUSION: Anti-CD19 CAR-modified T cells have shown therapeutic efficacy in patients with B-lineage malignancies and were well tolerated in most patients. Conditioning chemotherapy is a prerequisite to improve the clinical outcome.