PMID- 33605445
OWN - NLM
STAT- MEDLINE
DCOM- 20210924
LR  - 20210924
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Linking)
VI  - 193
IP  - 2
DP  - 2021 Apr
TI  - 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.
PG  - 325-338
LID - 10.1111/bjh.17326 [doi]
AB  - 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.
CI  - (c) 2021 The Authors. British Journal of Haematology published by British Society 
      for Haematology and John Wiley & Sons Ltd.
FAU - Stilgenbauer, Stephan
AU  - Stilgenbauer S
AUID- ORCID: 0000-0002-6830-9296
AD  - Department of Internal Medicine III, Ulm University, Ulm and Innere Medizin I, 
      Universitatsklinikum des Saarlandes, Homburg, Germany.
FAU - Bosch, Francesc
AU  - Bosch F
AD  - Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain.
FAU - Ilhan, Osman
AU  - Ilhan O
AD  - Internal Medical Sciences Departments, Ankara University School of Medicine, 
      Ankara, Turkey.
FAU - Kisro, Jens
AU  - Kisro J
AD  - Onkologische Schwerpunktpraxis Lubeck, Lubeck, Germany.
FAU - Mahe, Beatrice
AU  - Mahe B
AD  - Clinical Hematology, CHU Nantes Hotel-Dieu, Nantes, France.
FAU - Mikuskova, Eva
AU  - Mikuskova E
AD  - Department of Hemato-oncology II, National Cancer Institute, Bratislava, Slovakia 
      Blokhin.
FAU - Osmanov, Dzhelil
AU  - Osmanov D
AD  - Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russian 
      Federation.
FAU - Reda, Gianluigi
AU  - Reda G
AD  - UOC Ematologia - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 
      Milano, Italy.
FAU - Robinson, Sue
AU  - Robinson S
AD  - QEII Health Sciences Centre, Halifax, NS, Canada.
FAU - Tausch, Eugen
AU  - Tausch E
AD  - Department of Internal Medicine III, Ulm University, Ulm, Germany.
FAU - Turgut, Mehmet
AU  - Turgut M
AD  - Department of Internal Medical Sciences, Ondokuz Mayis University, Samsun, 
      Turkey.
FAU - Wojtowicz, Marcin
AU  - Wojtowicz M
AD  - Clinical Department of Hematology, Hematological Oncology and Internal Diseases, 
      Szpital Wojewodski, Opole, Poland.
FAU - Bottcher, Sebastian
AU  - Bottcher S
AD  - Department III of Internal Medicine, Rostock University Medical Center, Rostock 
      (current affiliation) and University Hospital Schleswig-Holstein, Kiel, Germany.
FAU - Perretti, Thomas
AU  - Perretti T
AD  - PDB Biostatistics -Medical Affairs, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Trask, Peter
AU  - Trask P
AD  - Patient Centered Outcomes Research, Genentech Inc, South San Francisco, CA, USA.
FAU - Van Hoef, Marlies
AU  - Van Hoef M
AD  - Global Product Development - Medical Affairs, F. Hoffmann-La Roche Ltd, Basel, 
      Switzerland.
FAU - Leblond, Veronique
AU  - Leblond V
AD  - Clinical Hematology, Sorbonne Universite, AP-HP Hopital Pitie Salpetriere, Paris, 
      France.
FAU - Foa, Robin
AU  - Foa R
AUID- ORCID: 0000-0002-5021-3026
AD  - Division of Hematology, Sapienza University, Rome, Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT01905943
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210219
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (Biomarkers, Pharmacological)
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - 18D0SL7309 (Chlorambucil)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - 981Y8SX18M (Bendamustine Hydrochloride)
RN  - FA2DM6879K (Vidarabine)
RN  - O43472U9X8 (obinutuzumab)
RN  - P2K93U8740 (fludarabine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Antineoplastic Agents, Immunological/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/therapeutic use
MH  - Bendamustine Hydrochloride/administration & dosage/adverse effects/therapeutic 
      use
MH  - Biomarkers, Pharmacological
MH  - Chlorambucil/administration & dosage/adverse effects/therapeutic use
MH  - Cyclophosphamide/administration & dosage/adverse effects/therapeutic use
MH  - Female
MH  - Humans
MH  - Immunoglobulin Heavy Chains/*drug effects/genetics
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Neoplasm, Residual/epidemiology
MH  - Neutropenia/chemically induced/epidemiology
MH  - Non-Randomized Controlled Trials as Topic
MH  - Progression-Free Survival
MH  - Recurrence
MH  - Safety
MH  - Thrombocytopenia/chemically induced/epidemiology
MH  - Treatment Outcome
MH  - Vidarabine/administration & dosage/adverse effects/analogs & 
      derivatives/therapeutic use
OTO - NOTNLM
OT  - IGHV
OT  - Obinutuzumab
OT  - chronic lymphocytic leukaemia
OT  - minimal residual disease
OT  - safety
EDAT- 2021/02/20 06:00
MHDA- 2021/09/25 06:00
CRDT- 2021/02/19 08:40
PHST- 2020/10/23 00:00 [received]
PHST- 2020/12/21 00:00 [accepted]
PHST- 2021/02/20 06:00 [pubmed]
PHST- 2021/09/25 06:00 [medline]
PHST- 2021/02/19 08:40 [entrez]
AID - 10.1111/bjh.17326 [doi]
PST - ppublish
SO  - Br J Haematol. 2021 Apr;193(2):325-338. doi: 10.1111/bjh.17326. Epub 2021 Feb 19.