Work

Venetoclax Plus Rituximab for Relapse/Refractory Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-analysis of Treatments Available in Brazil

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: 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. Chronic lymphocytic leukemia (CLL) that returns after treatment or does not respond well to available medications, known as relapsed or refractory CLL, remains a therapeutic challenge, especially for patients who have already undergone multiple previous treatments. Venetoclax has shown promising results in this population. In this study, we evaluated the efficacy and safety of venetoclax, used in combination with rituximab, compared with other treatments approved for relapsed or refractory CLL (RR-CLL) in Brazil. We conducted a literature review of clinical studies evaluating the efficacy of RR-CLL treatments that were directly compared within the same trials. We also performed a statistical analysis to compare treatments indirectly, since most treatments had not been directly compared in the studies. The main objectives assessed were patient survival time, duration of disease control, treatment response rates, and the occurrence of serious side effects. Across the available 12 trials, the venetoclax plus rituximab combination showed better disease control and longer survival compared with several other treatments, with similar side effects. However, the certainty of these results is still limited because the studies had important differences between them. Nevertheless, these findings help guide treatment decisions for people with RR-CLL, highlighting the role of venetoclax and also other drugs in the same class, such as Bruton’s tyrosine kinase inhibitors.

Source: Oncology and Therapy

DOI: 10.1007/s40487-026-00418-x