Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study.

Abstract

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: Franck Andre Morschhauser, Guillaume Cartron, Catherine Thieblemont, Philippe Solal-Céligny, Corinne Haioun, Reda Bouabdallah, Pierre Feugier, Krimo Bouabdallah, Elina Asikanius, Guiyuan Lei, Michael Wenger, Elisabeth Wassner-Fritsch, Gilles Andre Salles
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 31 Issue 23 Pg. 2912-9 (Aug 10 2013) ISSN: 1527-7755 [Electronic] United States
• PMID: 23835718 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• obinutuzumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects, pharmacokinetics)
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Drug Administration Schedule
• Female
• Humans
• Lymphoma, Large B-Cell, Diffuse (drug therapy, metabolism)
• Lymphoma, Mantle-Cell (drug therapy, metabolism)
• Male
• Middle Aged