Safety and Efficacy of Obinutuzumab Alone or with Chemotherapy in Previously Untreated or Relapsed/Refractory Chronic Lymphocytic Leukaemia Patients: Final Analysis of the Phase IIIb Green Study

Abstract

The manageable toxicity profile of obinutuzumab (GA101; G) alone or with chemotherapy in first-line (1L; fit and non-fit) and relapsed/refractory (R/R) patients with chronic lymphocytic leukaemia (CLL) was established in the primary analysis of the Phase IIIb GREEN trial (Clinicaltrials.gov: NCT01905943). The final analysis (cut-off, 31 January 2019) is reported here. Patients received G (1000 mg) alone (G-mono; fit and non-fit patients) or with chemotherapy [fludarabine and cyclophosphamide (FC; fit patients); chlorambucil (non-fit patients); bendamustine (any patient)]. Study endpoints were safety (primary) and efficacy (secondary). Subgroup analyses were performed on prognostic biomarkers in 1L CLL. Overall, 630 patients received 1L and 341 received R/R CLL treatment. At the final analysis, no new safety signals were observed [Grade >= 3 adverse events (AEs): 1L 82 center dot 7%, R/R 84 center dot 5%; serious AEs: 1L 58 center dot 1%, R/R 62 center dot 5%]. Neutropenia (1L 50 center dot 5%, R/R 53 center dot 4%) and thrombocytopenia (1L 14 center dot 6%, R/R 19 center dot 1%) were the most common Grade 3-5 AEs. G-mono-, G-bendamustine and G-FC-treated patients with unmutated immunoglobulin heavy chain trended towards shorter progression-free survival. Achievement of minimal residual disease negativity was greatest in 1L patients treated with G-FC. In this final analysis of the GREEN trial, the safety profile of G was consistent with current risk management strategies. Biomarker analyses supported efficacy in the specific subgroups.