PURPOSE:Obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, was superior to rituximab in human diffuse large B-cell lymphoma (DLBCL) and mantle-cell lymphoma (MCL) xenograft models. In phase I of our study, obinutuzumab (GA101) exhibited encouraging activity but no clear dose-response relationship, and few patients had aggressive histologies. The efficacy and safety of two doses of obinutuzumab (GA101) were explored in our randomized phase II trial in patients with heavily pretreated DBLCL and MCL. PATIENTS AND METHODS: Patients were randomly assigned to receive eight cycles of obinutuzumab (GA101) either as a flat dose of 400 mg for all infusions (days 1 and 8 of cycle 1; day 1 of cycles 2 to 8) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8. RESULTS:Forty patients were enrolled: 21 patients in the 400/400-mg treatment arm (DLBCL, n = 10; MCL, n = 11) and 19 patients in the 1,600/800-mg arm (DLBCL, n = 15; MCL, n = 4). End-of-treatment response was 28% (32% and 24% in the 1,600/800-mg and 400/400-mg study arms, respectively). Best overall response rates were 37% in the 1,600/800-mg arm and 24% in the 400/400-mg study arm (DLBCL, eight [32%] of 25 patients; MCL, four [27%] of 15 patients). Five (20%) of 25 rituximab-refractory patients exhibited treatment response, including four of 12 in the 1,600/800-mg group. The most common adverse events were infusion-related reactions (IRRs), which were manageable. Three patients had grade 3/4 IRRs. Grade 3/4 neutropenia was seen in only one patient. CONCLUSION:Obinutuzumab (GA101) 1,600/800 mg achieves early steady-state concentration and clinical activity with an acceptable safety profile in relapsed/refractory DLBCL and MCL, supporting further exploration.
RCT Entities:
PURPOSE:Obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, was superior to rituximab in human diffuse large B-cell lymphoma (DLBCL) and mantle-cell lymphoma (MCL) xenograft models. In phase I of our study, obinutuzumab (GA101) exhibited encouraging activity but no clear dose-response relationship, and few patients had aggressive histologies. The efficacy and safety of two doses of obinutuzumab (GA101) were explored in our randomized phase II trial in patients with heavily pretreated DBLCL and MCL. PATIENTS AND METHODS: Patients were randomly assigned to receive eight cycles of obinutuzumab (GA101) either as a flat dose of 400 mg for all infusions (days 1 and 8 of cycle 1; day 1 of cycles 2 to 8) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8. RESULTS: Forty patients were enrolled: 21 patients in the 400/400-mg treatment arm (DLBCL, n = 10; MCL, n = 11) and 19 patients in the 1,600/800-mg arm (DLBCL, n = 15; MCL, n = 4). End-of-treatment response was 28% (32% and 24% in the 1,600/800-mg and 400/400-mg study arms, respectively). Best overall response rates were 37% in the 1,600/800-mg arm and 24% in the 400/400-mg study arm (DLBCL, eight [32%] of 25 patients; MCL, four [27%] of 15 patients). Five (20%) of 25 rituximab-refractory patients exhibited treatment response, including four of 12 in the 1,600/800-mg group. The most common adverse events were infusion-related reactions (IRRs), which were manageable. Three patients had grade 3/4 IRRs. Grade 3/4 neutropenia was seen in only one patient. CONCLUSION:Obinutuzumab (GA101) 1,600/800 mg achieves early steady-state concentration and clinical activity with an acceptable safety profile in relapsed/refractory DLBCL and MCL, supporting further exploration.
Authors: E Van Den Neste; N Schmitz; N Mounier; D Gill; D Linch; M Trneny; N Milpied; J Radford; N Ketterer; O Shpilberg; U Dührsen; D Ma; J Brière; C Thieblemont; G Salles; C H Moskowitz; B Glass; C Gisselbrecht Journal: Bone Marrow Transplant Date: 2015-09-14 Impact factor: 5.483
Authors: Carla Casulo; Julie M Vose; William Y Ho; Brad Kahl; Mark Brunvand; Andre Goy; Yvette Kasamon; Bruce Cheson; Jonathan W Friedberg Journal: Clin Immunol Date: 2014-06-11 Impact factor: 3.969
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: Laurie H Sehn; Andre Goy; Fritz C Offner; Giovanni Martinelli; M Dolores Caballero; Ole Gadeberg; Tara Baetz; Andrew D Zelenetz; Gianluca Gaidano; Luis E Fayad; Rena Buckstein; Jonathan W Friedberg; Michael Crump; Branimir Jaksic; Pier Luigi Zinzani; Swaminathan Padmanabhan Iyer; Deniz Sahin; Akiko Chai; Günter Fingerle-Rowson; Oliver W Press Journal: J Clin Oncol Date: 2015-08-17 Impact factor: 44.544