Robert Marcus1, Andrew Davies1, Kiyoshi Ando1, Wolfram Klapper1, Stephen Opat1, Carolyn Owen1, Elizabeth Phillips1, Randeep Sangha1, Rudolf Schlag1, John F Seymour1, William Townsend1, Marek Trněný1, Michael Wenger1, Günter Fingerle-Rowson1, Kaspar Rufibach1, Tom Moore1, Michael Herold1, Wolfgang Hiddemann1. 1. From King's College Hospital (R.M.) and the Cancer Research UK and University College London Cancer Trials Centre (E.P., W.T.), London, and the Cancer Research UK Centre, University of Southampton, Southampton (A.D.) - all in the United Kingdom; the Tokai University School of Medicine, Isehara, Japan (K.A.); the University of Kiel, Kiel (W.K.), Gemeinschaftspraxis, Würzburg (R. Schlag), HELIOS Klinikum Erfurt, Erfurt (M.H.), and the Ludwig-Maximilians-University Hospital Grosshadern, Munich (W.H.) - all in Germany; Monash Health and Monash University (S.O.) and the Peter MacCallum Cancer Centre and University of Melbourne (J.F.S.), Melbourne, VIC, Australia; Foothills Medical Centre and Tom Baker Cancer Centre, Calgary, AB (C.O.), and the Cross Cancer Institute, Edmonton, AB (R. Sangha) - both in Canada; Charles University, Prague, Czech Republic (M.T.); and F. Hoffmann-La Roche, Basel, Switzerland (M.W., G.F.-R., K.R., T.M.).
Abstract
BACKGROUND:Rituximab-based immunochemotherapy has improved outcomes in patients with follicular lymphoma. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody. We compared rituximab-based chemotherapy with obinutuzumab-based chemotherapy in patients with previously untreated advanced-stage follicular lymphoma. METHODS: We randomly assigned patients to undergo induction treatment with obinutuzumab-based chemotherapy or rituximab-based chemotherapy. Patients with a response received maintenance treatment for up to 2 years with the same antibody that they had received in induction. The primary end point was investigator-assessed progression-free survival. RESULTS: A total of 1202 patients with follicular lymphoma underwent randomization (601 patients in each group). After a median follow-up of 34.5 months (range, 0 to 54.5), a planned interim analysis showed that obinutuzumab-based chemotherapy resulted in a significantly lower risk of progression, relapse, or death than rituximab-based chemotherapy (estimated 3-year rate of progression-free survival, 80.0% vs. 73.3%; hazard ratio for progression, relapse, or death, 0.66; 95% confidence interval [CI], 0.51 to 0.85; P=0.001). Similar results were seen with regard to independently reviewed progression-free survival and other time-to-event end points. Response rates were similar in the two groups (88.5% in the obinutuzumab group and 86.9% in the rituximab group). Adverse events of grade 3 to 5 were more frequent in the obinutuzumab group than in the rituximab group (74.6% vs. 67.8%), as were serious adverse events (46.1% vs. 39.9%). The rates of adverse events resulting in death were similar in the two groups (4.0% in the obinutuzumab group and 3.4% in the rituximab group). The most common adverse events were infusion-related events that were considered by the investigators to be largely due to obinutuzumab in 353 of 595 patients (59.3%; 95% CI, 55.3 to 63.2) and to rituximab in 292 of 597 patients (48.9%; 95% CI, 44.9 to 52.9; P<0.001). Nausea and neutropenia were common. A total of 35 patients (5.8%) in the obinutuzumab group and 46 (7.7%) in the rituximab group died. CONCLUSIONS:Obinutuzumab-based immunochemotherapy and maintenance therapy resulted in longer progression-free survival than rituximab-based therapy. High-grade adverse events were more common with obinutuzumab-based chemotherapy. (Funded by F. Hoffmann-La Roche; GALLIUM ClinicalTrials.gov number, NCT01332968 .).
RCT Entities:
BACKGROUND:Rituximab-based immunochemotherapy has improved outcomes in patients with follicular lymphoma. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody. We compared rituximab-based chemotherapy with obinutuzumab-based chemotherapy in patients with previously untreated advanced-stage follicular lymphoma. METHODS: We randomly assigned patients to undergo induction treatment with obinutuzumab-based chemotherapy or rituximab-based chemotherapy. Patients with a response received maintenance treatment for up to 2 years with the same antibody that they had received in induction. The primary end point was investigator-assessed progression-free survival. RESULTS: A total of 1202 patients with follicular lymphoma underwent randomization (601 patients in each group). After a median follow-up of 34.5 months (range, 0 to 54.5), a planned interim analysis showed that obinutuzumab-based chemotherapy resulted in a significantly lower risk of progression, relapse, or death than rituximab-based chemotherapy (estimated 3-year rate of progression-free survival, 80.0% vs. 73.3%; hazard ratio for progression, relapse, or death, 0.66; 95% confidence interval [CI], 0.51 to 0.85; P=0.001). Similar results were seen with regard to independently reviewed progression-free survival and other time-to-event end points. Response rates were similar in the two groups (88.5% in the obinutuzumab group and 86.9% in the rituximab group). Adverse events of grade 3 to 5 were more frequent in the obinutuzumab group than in the rituximab group (74.6% vs. 67.8%), as were serious adverse events (46.1% vs. 39.9%). The rates of adverse events resulting in death were similar in the two groups (4.0% in the obinutuzumab group and 3.4% in the rituximab group). The most common adverse events were infusion-related events that were considered by the investigators to be largely due to obinutuzumab in 353 of 595 patients (59.3%; 95% CI, 55.3 to 63.2) and to rituximab in 292 of 597 patients (48.9%; 95% CI, 44.9 to 52.9; P<0.001). Nausea and neutropenia were common. A total of 35 patients (5.8%) in the obinutuzumab group and 46 (7.7%) in the rituximab group died. CONCLUSIONS:Obinutuzumab-based immunochemotherapy and maintenance therapy resulted in longer progression-free survival than rituximab-based therapy. High-grade adverse events were more common with obinutuzumab-based chemotherapy. (Funded by F. Hoffmann-La Roche; GALLIUM ClinicalTrials.gov number, NCT01332968 .).
Authors: Brian T Hill; Loretta Nastoupil; Allison M Winter; Melody R Becnel; James R Cerhan; Thomas M Habermann; Brian K Link; Matthew J Maurer; Bita Fakhri; Prathima Reddy; Stephen D Smith; Dhruvika Mukhija; Deepa Jagadeesh; Amrita Desai; Juan Pablo Alderuccio; Izidore S Lossos; Pooja Mehra; Craig A Portell; Max L Goldman; Oscar Calzada; Jonathon B Cohen; Mohammad J Hussain; Nilanjan Ghosh; Paolo Caimi; Timothy Tiutan; Peter Martin; Abhigna Kodali; Andrew M Evens; Brad S Kahl Journal: Br J Haematol Date: 2018-12-21 Impact factor: 6.998
Authors: Diego Villa; Laurie H Sehn; Kerry J Savage; Cynthia L Toze; Kevin Song; Wendie D den Brok; Ciara L Freeman; David W Scott; Alina S Gerrie Journal: Blood Adv Date: 2020-08-11
Authors: Sarah C Rutherford; Michael Herold; Wolfgang Hiddemann; Lale Kostakoglu; Robert Marcus; Maurizio Martelli; Laurie H Sehn; Marek Trněný; Judith Trotman; Umberto Vitolo; Tina Nielsen; Federico Mattiello; Deniz Sahin; Gila Sellam; Peter Martin Journal: Blood Adv Date: 2020-04-28
Authors: Jeff P Sharman; Andres Forero-Torres; Luciano J Costa; Ian W Flinn; Lowell Inhorn; Kevin Kelly; Alberto Bessudo; Luis E Fayad; Mark S Kaminski; Andrew M Evens; Christopher R Flowers; Deniz Sahin; Kirsten E Mundt; Thomas Sandmann; Günter Fingerle-Rowson; Charlotte Vignal; Mehrdad Mobasher; Andrew D Zelenetz Journal: Leuk Lymphoma Date: 2018-10-02
Authors: Gita Thanarajasingam; Lori M Minasian; Frederic Baron; Franco Cavalli; R Angelo De Claro; Amylou C Dueck; Tarec C El-Galaly; Neil Everest; Jan Geissler; Christian Gisselbrecht; John Gribben; Mary Horowitz; S Percy Ivy; Caron A Jacobson; Armand Keating; Paul G Kluetz; Aviva Krauss; Yok Lam Kwong; Richard F Little; Francois-Xavier Mahon; Matthew J Matasar; María-Victoria Mateos; Kristen McCullough; Robert S Miller; Mohamad Mohty; Philippe Moreau; Lindsay M Morton; Sumimasa Nagai; Simon Rule; Jeff Sloan; Pieter Sonneveld; Carrie A Thompson; Kyriaki Tzogani; Flora E van Leeuwen; Galina Velikova; Diego Villa; John R Wingard; Sophie Wintrich; John F Seymour; Thomas M Habermann Journal: Lancet Haematol Date: 2018-06-18 Impact factor: 18.959