PMID- 29749403
OWN - NLM
STAT- MEDLINE
DCOM- 20190521
LR  - 20231103
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 32
IP  - 8
DP  - 2018 Aug
TI  - Obinutuzumab plus bendamustine in previously untreated patients with CLL: a 
      subgroup analysis of the GREEN study.
PG  - 1778-1786
LID - 10.1038/s41375-018-0146-5 [doi]
AB  - GREEN (NCT01905943) is a non-randomized, open-label phase IIIb study 
      investigating obinutuzumab alone or plus chemotherapy in chronic lymphocytic 
      leukemia (CLL). We report a preplanned subgroup analysis of 158 previously 
      untreated CLL patients receiving obinutuzumab-bendamustine (G-B). Patients 
      received six 28-day cycles (C) of G-B: obinutuzumab day (D)1/D2 of C1 (25 mg 
      D1/975 mg D2), 1000 mg D8 and D15 of C1, and D1 of C2-6; and bendamustine 
      70/90 mg/m(2) D1 and D2 of C1-6. The primary endpoint was safety/tolerability. 
      Grade >/=3 adverse events (AEs) occurred in 82.3% of patients, including 
      neutropenia (49.4%), thrombocytopenia (12.0%) and febrile neutropenia (10.8%). 
      Serious AEs included neutropenia (12.7%), febrile neutropenia (9.5%) and 
      pneumonia (7.6%). Rates of grade >/=3 infections and infusion-related reactions 
      were 20.3% and 17.1%, respectively. Due to tumor lysis syndrome (TLS; 8.2%), 
      including two associated fatalities (one in another study cohort), additional 
      risk-minimization measures were implemented. Overall response rate was 81.0%. 
      After 32.8 months' median observation time, 2-year progression-free survival was 
      81.8%. Minimal residual disease was undetectable in 59.5% (94/158) and 27.8% 
      (44/158) of patients for blood and bone marrow, respectively. Frontline G-B 
      appears to have manageable toxicity with clinical activity in CLL. Careful TLS 
      risk assessment, pretreatment and monitoring is required.
FAU - Stilgenbauer, Stephan
AU  - Stilgenbauer S
AD  - Department of Internal Medicine III, Ulm University, Ulm, Germany. 
      Stephan.Stilgenbauer@uniklinik-ulm.de.
AD  - Klinik fur Innere Medizin I, Universitatsklinikum des Saarlandes, Homburg, 
      Germany. Stephan.Stilgenbauer@uniklinik-ulm.de.
FAU - Leblond, Veronique
AU  - Leblond V
AD  - UPMC GRC11-GRECHY, AP-HP Hopital Pitie Salpetriere, Paris, France.
FAU - Foa, Robin
AU  - Foa R
AD  - Department of Cellular Biotechnologies and Hematology, 'Sapienza' University, 
      Rome, Italy.
FAU - Bottcher, Sebastian
AU  - Bottcher S
AD  - Second Department of Medicine, University of Schleswig-Holstein, Campus Kiel, 
      Kiel, Germany.
AD  - Clinic III, Hematology, Oncology and Palliative Medicine, University of Rostock, 
      Rostock, Germany.
FAU - Ilhan, Osman
AU  - Ilhan O
AD  - Ankara University, Ankara, Turkey.
FAU - Knauf, Wolfgang
AU  - Knauf W
AD  - Onkologische Gemeinschaftspraxis, Agaplesion Bethanien Krankenhaus, Frankfurt, 
      Germany.
FAU - Mikuskova, Eva
AU  - Mikuskova E
AD  - National Cancer Institute, Bratislava, Slovakia.
FAU - Renner, Christoph
AU  - Renner C
AD  - OnkoZentrum Zurich, Zurich, Switzerland.
FAU - Tausch, Eugen
AU  - Tausch E
AD  - Department of Internal Medicine III, Ulm University, Ulm, Germany.
FAU - Woszczyk, Dariusz
AU  - Woszczyk D
AD  - State Hospital, Opole, Poland.
AD  - Haematology Department, University of Opole, Provincial Hospital, Opole, Poland.
FAU - Gresko, Ekaterina
AU  - Gresko E
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Lundberg, Linda
AU  - Lundberg L
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Moore, Tom
AU  - Moore T
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Morris, Thea
AU  - Morris T
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Robson, Susan
AU  - Robson S
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Bosch, Francesc
AU  - Bosch F
AD  - University Hospital Vall d'Hebron, Barcelona, Spain.
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 - 20180427
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 981Y8SX18M (Bendamustine Hydrochloride)
RN  - O43472U9X8 (obinutuzumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Bendamustine Hydrochloride/administration & dosage
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy/pathology
MH  - Neoplasm, Residual/*drug therapy/pathology
MH  - Prognosis
MH  - Remission Induction
MH  - Rituximab/administration & dosage
MH  - *Salvage Therapy
MH  - Survival Rate
PMC - PMC6087718
COIS- SS reports consulting fees, research funding, honoraria and membership of 
      advisory committees from Roche. VL reports speaker's bureau fees, consulting 
      fees, research funding, honoraria and membership of advisory committees from 
      Roche; speaker's bureau fees, consulting fees, honoraria and membership of 
      advisory committees from Janssen; speaker's bureau fees, honoraria and membership 
      of advisory committees from Gilead and GSK; membership of advisory committees for 
      AbbVie; and speaker's bureau fees from Mundipharma. RF reports speaker's bureau 
      fees, consulting fees, honoraria and membership of advisory committees from 
      Roche, Janssen, Celgene, AbbVie, Amgen and Novartis. SB reports consulting fees 
      from Roche and AbbVie; research funding from Roche, AbbVie and Celgene; and 
      honoraria from Roche, AbbVie and Beckton Dickinson. WK reports honoraria and 
      participation in advisory boards for Roche and Mundipharma. CR reports research 
      funding and membership of advisory committees from Roche and Celgene. FB reports 
      consulting fees and honoraria from Roche, Novartis, Janssen, AbbVie, Gilead and 
      Mundipharma; and research funding from Roche and Janssen. OI, EM, ET and DW 
      report research funding from Roche. EG, LL, T Moore, T Morris and SR report 
      employment from Roche.
EDAT- 2018/05/12 06:00
MHDA- 2019/05/22 06:00
PMCR- 2018/04/27
CRDT- 2018/05/12 06:00
PHST- 2017/11/22 00:00 [received]
PHST- 2018/03/28 00:00 [accepted]
PHST- 2018/03/13 00:00 [revised]
PHST- 2018/05/12 06:00 [pubmed]
PHST- 2019/05/22 06:00 [medline]
PHST- 2018/05/12 06:00 [entrez]
PHST- 2018/04/27 00:00 [pmc-release]
AID - 10.1038/s41375-018-0146-5 [pii]
AID - 146 [pii]
AID - 10.1038/s41375-018-0146-5 [doi]
PST - ppublish
SO  - Leukemia. 2018 Aug;32(8):1778-1786. doi: 10.1038/s41375-018-0146-5. Epub 2018 Apr 
      27.