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.