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Ferrata Storti Foundation
Haematologica 2019 Volume 104(6):1202-1208
Non-Hodgkin Lymphoma
Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression
John F. Seymour,1 Robert Marcus,2 Andrew Davies,3 Eve Gallop-Evans,4 Andrew Grigg,5 Andrew Haynes,6 Michael Herold,7 Thomas Illmer,8 Herman Nilsson-Ehle,9 Martin Sökler,10 Ulrich Dünzinger,11 Tina Nielsen,12 Aino Launonen12 and Wolfgang Hiddemann13
1
Peter MacCallum Cancer Centre, Royal Melbourne Hospital and University of Melbourne,
Victoria, Australia; 2Kings College Hospital, London, UK; 3Cancer Research UK Centre, University of Southampton, UK; 4Velindre Cancer Centre, Cardiff, UK; 5Austin Hospital, Melbourne, Victoria, Australia; 6Nottingham University Hospitals NHS Trust, UK; 7HELIOS-Klinikum Erfurt, Germany; 8BAG Freiberg-Richter, Jacobasch, Illmer and Wolf, Dresden, Germany; 9Section of Hematology and Coagulation, Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; 10Eberhard-Karls-University Tübingen, Germany; 11Roche Pharma AG, Grenzach-Wyhlen, Germany; 12F. Hoffmann-La Roche Ltd., Basel, Switzerland and 13Department of Medicine III, Ludwig-Maximilians- University, Munich, Germany
ABSTRACT
We evaluated early disease progression and its impact on overall survival (OS) in previously untreated follicular lymphoma patients in GALLIUM (clinicaltrials.gov identifier: 01332968), and investigated the effect on early disease progression of the two randomiza- tion arms: obinutuzumab-based versus rituximab-based immunochemotherapy. Cause-specific Cox regression was used to estimate the effect of treatment on the risk of disease progression or death due to disease progression within 24 months of randomization and to ana- lyze OS in patients with or without disease progression after 24 months. Mortality in both groups was analyzed 6, 12, and 18 months post random- ization (median follow up, 41 months). Fewer early disease progression events occurred in obinutuzumab (57 out of 601) versus rituximab (98 out of 601) immunochemotherapy patients, with an average risk reduction of 46.0% (95%CI: 25.0-61.1%; cumulative incidence rate 10.1% vs. 17.4%). At a median post-progression follow up of 22.6 months, risk of mortality increased markedly following a progression event [HR of time-varying pro- gression status, 25.5 (95%CI: 16.2-40.3)]. Mortality risk was higher the ear- lier patients progressed within the first 24 months. Age-adjusted HR for OS after 24 months in surviving patients with disease progression versus those without was 12.2 (95%CI: 5.6-26.5). Post-progression survival was similar by treatment arm. In conclusion, obinutuzumab plus chemotherapy was associated with a marked reduction in the rate of early disease progression events relative to rituximab plus chemotherapy. Early disease progression in patients with follicular lymphoma was associated with poor prognosis, with mortality risk higher after earlier progression. Survival post progres- sion did not seem to be influenced by treatment arm.
Introduction
Despite the favorable outcomes for patients with previously untreated follicular lymphoma (FL) that are now achievable with the current standard treatment of rit- uximab (R) plus chemotherapy (R-chemo) followed by R maintenance, 20-35% of patients still have progressive disease (PD), relapse, or death within two years.1-3
Correspondence:
JOHN SEYMOUR
john.seymour@petermac.org
Received: October 14, 2018. Accepted: December 17, 2018. Pre-published: December 20, 2018.
doi:10.3324/haematol.2018.209015
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/6/1202
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