PMID- 31455851 OWN - NLM STAT- MEDLINE DCOM- 20200804 LR - 20240328 IS - 1476-5551 (Electronic) IS - 0887-6924 (Print) IS - 0887-6924 (Linking) VI - 34 IP - 2 DP - 2020 Feb TI - Obinutuzumab plus fludarabine and cyclophosphamide in previously untreated, fit patients with chronic lymphocytic leukemia: a subgroup analysis of the GREEN study. PG - 441-450 LID - 10.1038/s41375-019-0554-1 [doi] AB - GREEN (NCT01905943) is a nonrandomized, open-label, single-arm, phase 3b study investigating the safety and efficacy of obinutuzumab alone or in combination with chemotherapy in chronic lymphocytic leukemia (CLL). We report the preplanned subgroup analysis of 140 previously untreated, fit CLL patients who received obinutuzumab plus fludarabine and cyclophosphamide (G-FC). The primary endpoint was safety and tolerability. Efficacy was the secondary endpoint. Obinutuzumab 1000 mg was administered intravenously on Day (D)1 (dose split D1‒2), D8 and D15 of Cycle (C)1, and D1 of C2-6 (28-day cycles). Standard intravenous/oral doses of fludarabine and cyclophosphamide were administered on D1-3 of C1-6. Overall, 87.1% of patients experienced grade >/= 3 adverse events (AEs), including neutropenia (67.1%) and thrombocytopenia (17.1%). Serious AEs were experienced by 42.1% of patients. Rates of grade >/= 3 infusion-related reactions and infections were 19.3% and 15.7%, respectively. Overall response rate was observed in 90.0%, with 46.4% of patients achieving complete response (CR; including CR with incomplete marrow recovery). Minimal residual disease negativity rates were 64.3% in peripheral blood and 35.7% in bone marrow (intent-to-treat analysis). After a median observation time of 25.6 months, 2 year progression-free survival was 91%. Frontline G-FC represents a promising treatment option for fit patients with CLL. FAU - Bosch, Francesc AU - Bosch F AUID- ORCID: 0000-0001-9241-2886 AD - University Hospital Vall d'Hebron, Barcelona, Spain. fbosch@vhio.net. FAU - Cantin, Guy AU - Cantin G AD - Hopital De L'Enfant-Jesus, Quebec City, QC, Canada. FAU - Cortelezzi, Agostino AU - Cortelezzi A AD - Hematology Unit, Policlinico Hospital and University of Milan, Milan, Italy. FAU - Knauf, Wolfgang AU - Knauf W AD - Onkologische Gemeinschaftspraxis, Agaplesion Bethanien Krankenhaus, Frankfurt, Germany. FAU - Tiab, Mourad AU - Tiab M AD - University Hospital, La Roche Sur Yon, France. FAU - Turgut, Mehmet AU - Turgut M AD - Ondokuz Mayis University, Samsun, Turkey. FAU - Zaritskey, Andrey AU - Zaritskey A AD - Almazov National Medical Research Center, St Petersburg, Russia. FAU - Merot, Jean-Louis AU - Merot JL AD - IQVIA, St Ouen, France. FAU - Tausch, Eugen AU - Tausch E AD - Department of Internal Medicine III, Ulm University, Ulm and Innere Medizin I, Universitatsklinikum des Saarlandes, Homburg, Germany. FAU - Trunzer, Kerstin AU - Trunzer K AD - F. Hoffmann-La Roche Ltd, Basel, Switzerland. FAU - Robson, Susan AU - Robson S AD - F. Hoffmann-La Roche Ltd, Basel, Switzerland. FAU - Gresko, Ekaterina AU - Gresko E AD - F. Hoffmann-La Roche Ltd, Basel, Switzerland. FAU - Bottcher, Sebastian AU - Bottcher S AD - Second Department of Medicine, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany and Clinic III, Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, Rostock, Germany. FAU - Foa, Robin AU - Foa R AD - Hematology, Sapienza University, Rome, Italy. FAU - Stilgenbauer, Stephan AU - Stilgenbauer S AD - Department of Internal Medicine III, Ulm University, Ulm and Innere Medizin I, Universitatsklinikum des Saarlandes, Homburg, Germany. FAU - Leblond, Veronique AU - Leblond V AD - Sorbonne Universite, AP-HP Hopital Pitie Salpetriere, Paris, France. 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 - 20190827 PL - England TA - Leukemia JT - Leukemia JID - 8704895 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 8N3DW7272P (Cyclophosphamide) RN - FA2DM6879K (Vidarabine) RN - O43472U9X8 (obinutuzumab) RN - P2K93U8740 (fludarabine) SB - IM MH - Adult MH - Aged MH - Antibodies, Monoclonal, Humanized/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Cyclophosphamide/administration & dosage MH - Female MH - Humans MH - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy MH - Male MH - Middle Aged MH - Progression-Free Survival MH - Remission Induction/methods MH - Vidarabine/administration & dosage/analogs & derivatives PMC - PMC7214269 COIS- FB reports: consultancy, honoraria, and speakers bureau for Roche, Novartis, Janssen, Abbvie, Gilead, and Mundipharma; research funding from Roche, Celgene, Karyospharm, and Takeda; AZ reports: consultancy for Novartis and Janssen; speakers bureau for Novartis; J-LM and ET reports: research funding from Roche; KT reports: employment and equity ownership for Roche; SR reports: employment for Roche; EG reports: former employment for Roche; SB reports consulting fees from Roche and AbbVie; research funding from Roche, AbbVie, Janssen, and Celgene; and honoraria from Roche, AbbVie, Novartis, Janssen, and Becton Dickinson; SS reports: honoraria, consultancy, advisory board membership, travel support, research funding, and speakers bureau for AbbVie, Amgen, Celgene, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pharmacyclics, and Roche; RF reports: consultancy and speakers bureau for Roche, Janssen, Gilead, Amgen, Celgene, BMS, Sandoz, Novartis, and Abbvie; VL reports: honoraria for Abbvie, Roche, Gilead, Janssen, BMS, Novartis, and Servier; advisory board membership for Abbvie, Roche, Gilead, Janssen, Novartis, and Servier; speakers bureau for Abbvie and Janssen; MT reports: advisory board membership, speaker bureau, and research funding from Roche; WK reports honoraria from Roche; GC, AC, and MT report no conflicts of interest. EDAT- 2019/08/29 06:00 MHDA- 2020/08/05 06:00 PMCR- 2019/08/27 CRDT- 2019/08/29 06:00 PHST- 2019/03/28 00:00 [received] PHST- 2019/07/04 00:00 [accepted] PHST- 2019/06/21 00:00 [revised] PHST- 2019/08/29 06:00 [pubmed] PHST- 2020/08/05 06:00 [medline] PHST- 2019/08/29 06:00 [entrez] PHST- 2019/08/27 00:00 [pmc-release] AID - 10.1038/s41375-019-0554-1 [pii] AID - 554 [pii] AID - 10.1038/s41375-019-0554-1 [doi] PST - ppublish SO - Leukemia. 2020 Feb;34(2):441-450. doi: 10.1038/s41375-019-0554-1. Epub 2019 Aug 27.