OBJECTIVES: Obinutuzumab (GA101) is a novel, glycoengineered, type II CD20 antibody. In the phase 3 CLL11 trial, chlorambucil (Clb) plus GA101 (G-Clb) significantly prolonged progression-free survival (PFS) compared with either Clb alone or rituximab plus Clb in previously untreated patients with chronic lymphocytic leukemia (CLL) and comorbidities. We present indirect treatment comparisons (ITCs) of G-Clb versus bendamustine (Benda), and ofatumumab plus Clb (Ofat-Clb). METHODS: We conducted a systematic review of non-randomized and randomized controlled trials (RCTs) to assess the clinical efficacy and safety of pharmacological interventions for previously untreated CLL; manuscripts (Jan 1992 to Mar 2013), abstracts (including hand-searching; Jan 2010 to Mar 2013), and in-progress trials were screened for inclusion. Based on extracted data, a feasibility assessment of quantitative analysis was undertaken. ITCs of G-Clb versus Benda and G-Clb versus Ofat-Clb were derived. The WinBUGS code used to parameterize the fixed-effect network meta-analysis model used a natural logarithm of the hazard ratios (HR) for PFS as the (continuous) outcome variable. RESULTS: Of the 4,819 publications identified, 262 manuscripts and 13 abstracts were selected for detailed evaluation. Following de-duplication of publications, the data set included 28 RCTs (157 publications) and nine non-RCTs (14 publications). ITCs were based on HR and 95% confidence intervals (CIs) reported for G-Clb in the CLL11 trial, for Benda in the Knauf et al. publications, and for Ofat-Clb in the Complement 1 trial. The ITC for G-Clb versus Benda had a HR (95% CI) of 0.53 (0.35-0.77) and the ITC for G-Clb versus Ofat-Clb had a HR (95% CI) of 0.33 (0.22-0.47). CONCLUSIONS: Based on the ITCs of available evidence in this indication, G-Clb is expected to improve PFS rates compared with Benda or Ofat-Clb. How this benefit will translate into overall survival differences will be assessed when the available data are more mature.