Efficacy and Safety of B-cell Receptor Signaling Pathway Inhibitors in Relapsed/refractory Chronic Lymphocytic Leukemia: a Systematic Review and Meta-Analysis of Randomized Clinical Trials

Ibrutinib and idelalisib, B-cell receptor (BCR) signaling pathway inhibitors, have been recently approved for use against relapsed/refractory chronic lymphocytic leukemia (CLL). To assess the efficacy and safety of BCR pathway inhibitors in relapsed/refractory CLL, we conducted a systematic review and meta-analysis of five randomized controlled trials (1866 patients). Our study demonstrated that BCR pathway inhibitors significantly prolonged progression-free survival (PFS; pooled HR = 0.24; 95% CI: 0.19–0.30) and overall survival (HR = 0.58; 0.46–0.73) compared with control treatment. BCR pathway inhibitors increased the probability of response (RR = 3.54; 95% CI: 1.69–7.41) and decreased the risk of progression (RR = 0.21, 95% CI: 0.13–0.34). However, BCR pathway inhibitors increased the risk of grade 3 and 4 adverse events (AEs; RR = 1.25; 95% CI: 1.08–1.44) and serious AEs (RR = 1.32; 95% CI: 1.17–1.50). AEs causing discontinuation (RR = 1.26; 95% CI: 0.88–1.81) or death (RR = 1.06; 95% CI: 0.72–1.57) were not significantly increased. No statistically significant difference in any aspect of meta-analysis was noted between ibrutinib and idelalisib.