Venetoclax Plus Rituximab for Relapse/Refractory Chronic Lymphocytic Leukemia: A Systematic Review and Network...

Venetoclax represents a significant advancement in target anticancer therapy in the management of relapsed/refractory chronic lymphocytic leukemia (RR-CLL). This study aims to compare the efficacy and safety of the venetoclax + rituximab (VenR) regimen with other therapies approved in Brazil.

A systematic review and network meta-analysis (NMA) was conducted to evaluate the efficacy and safety of treatments approved in Brazil for RR-CLL. Comprehensive literature searches were performed to identify randomized controlled trials. Risk of bias and certainty of evidence for each outcome were assessed across the included studies. The NMA was conducted using a frequentist framework. The primary efficacy outcomes were progression-free survival, overall survival, overall response rate, and time to next therapy. Safety was assessed on the basis of the incidence of serious adverse events.

A total of 24 publications related to 12 trials were identified and included. VenR was associated with better survival outcomes when compared with standard regimens such as rituximab (HR 0.16; 95% CI 0.03-0.74) and physician choice (HR 0.17; 95% CI 0.04-0.81). In terms of progression-free survival, VenR achieved HR < 0.20, supported by narrow confidence intervals, when compared to treatments such as bendamustine plus rituximab, ofatumumab and physician choice, in addition to significantly favorable results compared to ibrutinib and acalabrutinib. Approximately half of the studies presented a low risk of bias, and the certainty of evidence assessed using the GRADE-NMA approach resulted in very low certainty of evidence, mainly due to risk of bias, intransitivity, and imprecision.

This NMA provides valuable evidence to support rational therapeutic choices for RR-CLL in Brazil, highlighting VenR and Bruton tyrosine kinase inhibitors as leading treatment options across diverse clinical scenarios.