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.
Keywords:
IGHV; Obinutuzumab; chronic lymphocytic leukaemia; minimal residual disease; safety.
© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
Publication types
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Clinical Trial, Phase III
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Multicenter Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Antibodies, Monoclonal, Humanized / administration & dosage
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Antibodies, Monoclonal, Humanized / adverse effects
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Antibodies, Monoclonal, Humanized / therapeutic use*
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Antineoplastic Agents, Immunological / administration & dosage
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Antineoplastic Agents, Immunological / adverse effects
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Antineoplastic Agents, Immunological / therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Bendamustine Hydrochloride / administration & dosage
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Bendamustine Hydrochloride / adverse effects
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Bendamustine Hydrochloride / therapeutic use
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Biomarkers, Pharmacological
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Chlorambucil / administration & dosage
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Chlorambucil / adverse effects
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Chlorambucil / therapeutic use
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Cyclophosphamide / administration & dosage
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Cyclophosphamide / adverse effects
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Cyclophosphamide / therapeutic use
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Female
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Humans
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Immunoglobulin Heavy Chains / drug effects*
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Immunoglobulin Heavy Chains / genetics
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Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
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Male
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Middle Aged
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Neoplasm, Residual / epidemiology
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Neutropenia / chemically induced
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Neutropenia / epidemiology
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Non-Randomized Controlled Trials as Topic
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Progression-Free Survival
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Recurrence
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Safety
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Thrombocytopenia / chemically induced
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Thrombocytopenia / epidemiology
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Treatment Outcome
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Vidarabine / administration & dosage
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Vidarabine / adverse effects
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Vidarabine / analogs & derivatives
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Vidarabine / therapeutic use
Substances
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents, Immunological
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Biomarkers, Pharmacological
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Immunoglobulin Heavy Chains
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Chlorambucil
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Cyclophosphamide
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Bendamustine Hydrochloride
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Vidarabine
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obinutuzumab
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fludarabine
Associated data
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ClinicalTrials.gov/NCT01905943