Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study

Abstract

Purpose: Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab with rituximab in relapsed indolent lymphoma. The primary end point of this study was the overall response rate (ORR) in patients with follicular lymphoma after induction and safety in patients with indolent lymphoma.

Patients and methods: A total of 175 patients with relapsed CD20(+) indolent lymphoma requiring therapy and with previous response to a rituximab-containing regimen were randomly assigned (1:1) to four once-per-week infusions of either obinutuzumab (1,000 mg) or rituximab (375 mg/m(2)). Patients without evidence of disease progression after induction therapy received obinutuzumab or rituximab maintenance therapy every 2 months for up to 2 years.

Results: Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab (44.6% v 26.7%; P = .01). However, this difference did not translate into an improvement in progression-free survival. No new safety signals were observed for obinutuzumab, and the incidence of adverse events was balanced between arms, with the exception of infusion-related reactions and cough, which were higher in the obinutuzumab arm.

Conclusion: Obinutuzumab demonstrated a higher ORR without appreciable differences in safety compared with rituximab. However, the clinical benefit of obinutuzumab in this setting remains unclear and should be evaluated within phase III trials.

Trial registration: ClinicalTrials.gov NCT00576758.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2015 by American Society of Clinical Oncology.

Figures

Fig 1.

CONSORT diagram of patients with follicular non-Hodgkin lymphoma. AE, adverse event; PD, progressive disease.

Fig 2.

Progression-free survival of patients with follicular lymphoma treated with obinutuzumab versus rituximab monotherapy.

Fig A1.

Mean (± standard deviation) obinutuzumab serum concentrations in patients with indolent non-Hodgkin lymphoma after once-per-week administration of 1,000 mg obinutuzumab during the four-cycle induction period. Error bars represent the standard deviation.

Fig A2.

Mean (± standard deviation) obinutuzumab serum concentrations in patients with indolent non-Hodgkin lymphoma after once-per-week administration of 1,000 mg obinutuzumab during the four-cycle induction period and during 11 cycles of maintenance regimen, which consisted of once-every-2-months administration of 1,000 mg obinutuzumab. Error bars represent the standard deviation.

Fig A3.

Median serum concentrations of (A) interleukin-6 (IL-6), (B) IL-8, and (C) IL-10 in patients with indolent non-Hodgkin lymphoma after once-per-week administration of 1,000 mg obinutuzumab or 375 mg/m2 rituximab during the four-cycle induction period. C, cycle; D, day; End, end of infusion; Mid, midinfusion; Post, postinfusion; Pre, preinfusion.