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

Abstract

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.

Keywords:

• Chronic lymphocytic leukemia
• ibrutinib
• idelalisib
• meta-analysis

Acknowledgments

On behalf of our team, we would like to thank the authors of the randomized clinical trials who gracefully shared with us their manuscripts in order to facilitate the comprehensiveness of this meta-analysis.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1375101.

Additional information

Funding

The study was supported in part by funding from the Medical University of Lodz, Poland [503/8-093-01/503-01].