Efficacy of Venetoclax+Obinutuzumab+Ibrutinib Compared to Alternative Therapeutic Options in the First-Line Treatment of Chronic Lymphocytic Leukemia (Fit Population): A Systematic Review and Network Meta-Analysis

OBJECTIVES: Venetoclax+obinutuzumab+ibrutinib (VEN+OBI+IBR) is a new anti-leukemic regimen for patients with treatment-naïve chronic lymphocytic leukemia (TN CLL), superior to chemoimmunotherapy (FCR / BEND+RTX) based on the results of the CLL13 trial (GAIA). However, the relative efficacy and safety of VEN+OBI+IBR compared to other treatment options remain unknown. The aim of this study was to assess the efficacy of VEN+OBI+IBR versus alternative targeted therapy regimens including IBR+RTX, IBR+VEN and VEN+OBI, in the patients with TN CLL suitable to receive fludarabine chemotherapy (fit population).

METHODS: A systematic review was performed using the most important medical databases (MEDLINE, CENTRAL, EMBASE) and additional sources to identify randomized clinical trials for TN CLL (fit population) until May 2023 (PROSPERO: CRD42023393903). Data for the most similar and the longest available follow-up were used from identified studies to compare progression-free survival (PFS) in Bayesian network meta-analysis (NMA). The results of NMA were presented as hazard ratios (HR) with 95% confidence intervals (CI). The probability of the best treatment option was also calculated. Statistical analysis was performed using R and WinBUGS.

RESULTS: Six studies met the eligibility criteria and were included in the NMA. In the analysis considering the most similar follow-up PFS was comparable between VEN+OBI+IBR and other targeted therapy regimens (HR [95%CI] for VEN+OBI+IBR vs. IBR+RTX 1.00 [0.53, 1.89]; for VEN+OBI+IBR vs. IBR+VEN 0.95 [0.44, 2.08]; for VEN+OBI+IBR vs. VEN+OBI 0.74 [0.39, 1,42]). Similar results were obtained in the analysis for the longest follow-up available. In both analyses, VEN+OBI+IBR had the highest probability of being the best treatment option.

CONCLUSIONS: The results of NMA suggest that VEN+OBI+IBR has similar efficacy versus other targeted therapy regimens in terms of PFS in TN CLL (fit population). However, it has the highest probability of being the best treatment option.