title: Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Hematology Department, EA 4481 GRIIOT, Centre Hospitalier Régional Universitaire de Lille, Lille, France. franck.morschhauser@chru-lille.fr
authors.forename: Franck Andre
authors.initials: FA
authors.lastname: Morschhauser
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cartron
authors.forename: Catherine
authors.initials: C
authors.lastname: Thieblemont
authors.forename: Philippe
authors.initials: P
authors.lastname: Solal-Céligny
authors.forename: Corinne
authors.initials: C
authors.lastname: Haioun
authors.forename: Reda
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: Pierre
authors.initials: P
authors.lastname: Feugier
authors.forename: Krimo
authors.initials: K
authors.lastname: Bouabdallah
authors.forename: Elina
authors.initials: E
authors.lastname: Asikanius
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Lei
authors.forename: Michael
authors.initials: M
authors.lastname: Wenger
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wassner-Fritsch
authors.forename: Gilles Andre
authors.initials: GA
authors.lastname: Salles
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000378:metabolism; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C543332:obinutuzumab