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

Stephan Stilgenbauer, Francesc Bosch, Osman Ilhan, Jens Kisro, Béatrice Mahé, Eva Mikuskova, Dzhelil Osmanov, Gianluigi Reda, Sue Robinson, Eugen Tausch, Mehmet Turgut, Marcin Wójtowicz, Sebastian Böttcher, Thomas Perretti, Peter Trask, Marlies Van Hoef, Véronique Leblond, Robin Foà

Research output: Contribution to journalArticlepeer-review

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 82·7%, R/R 84·5%; serious AEs: 1L 58·1%, R/R 62·5%]. Neutropenia (1L 50·5%, R/R 53·4%) and thrombocytopenia (1L 14·6%, R/R 19·1%) 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.

Original languageEnglish
Pages (from-to)325-338
Number of pages14
JournalBritish Journal of Haematology
Volume193
Issue number2
DOIs
Publication statusPublished - Apr 2021

Keywords

  • chronic lymphocytic leukaemia
  • IGHV
  • minimal residual disease
  • Obinutuzumab
  • safety

ASJC Scopus subject areas

  • Hematology

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