For more than 10 years, rituximab has held a unique place in the treatment of a range of B-cell lymphomas. But a new “glycoengineered” humanized monoclonal antibody is entering the treatment arena, and data presented at ASH 2011 set the stage for phase 3 testing against the long-term standard of care.
In patients with relapsed indolent non-Hodgkin lymphoma (NHL), the CD20 inhibitor obinutuzumab (GA101) produced outcomes comparable to rituximab in the first head-to-head comparison of these drugs, Canadian investigators reported.
In the phase 2 GAUSS trial, induction therapy with obinutuzumab led to a higher overall response rate than induction with rituximab, according to an independent radiology review: 44.6% versus 26.7% (P = .01), including complete responses of 12.2% and 5.3%, respectively.
However, the primary end point—response rates according to local investigators—was not significantly different: 44.6% and 33.3% (P = .08), respectively, reported Laurie H. Sehn, MD, MPH, of the University of British Columbia, Vancouver.
Median progression-free survival was also similar between the arms at 17.3 months, with progression observed in 39.2% of obinutuzumab-treated patients and 34.7% of rituximab-treated patients.
According to Dr Sehn, the GAUSS trial was “not really designed to definitely answer if one agent is better. It is an attempt to get some comparisons and to determine if a randomized controlled trial is justifiable. The results imply a trend in benefit.”
In this open-label study, 175 patients (149 with follicular lymphoma and 26 with nonfollicular indolent NHL) were randomized to receive 4 weekly infusions with obinutuzumab or with rituximab. On average, patients had received 2 previous regimens, all with rituximab. Patients without evidence of disease progression after induction continued the regimen for up to 2 years.
Obinutuzumab was tolerable, but more infusion-related reactions were reported with it than with rituximab (74% vs 51%, respectively), including 11% and 6%, respectively, that were grade 3 or 4.
Additional data were presented from other phase 2 studies of patients with relapsed/refractory indolent NHL showing encouraging activity for obinutuzumab as a single agent and in combination with fludarabine and cyclophosphamide or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Responses were seen in patients with NHL refractory to rituximab.
At a press briefing, Dr Sehn said that “Unlike rituximab or other anti-CD20 agents in development, GA101 is a type 2 (humanized) monoclonal antibody. In preclinical testing, it has been shown to have a greater ability to directly cause cell death and to induce a greater immune-type reaction against the tumor. What is required now is to move this into trials to see if this translates into benefits for patients.”
Jane Winter, MD, of Northwestern University Feinberg School of Medicine, Chicago, moderated the press briefing. She commented, “This study shows how our new technologies are providing us with tools that are better than we have had before. Dr Sehn showed the benefit of bioengineering an antibody, which is different from serendipitously finding one that is effective.”
With the improved response rates and favorable toxicity profile, Dr Sehn and her colleagues concluded that, “phase 3 trials to truly test its efficacy are warranted.” Studies are now comparing obinutuzumab plus CHOP, or other regimens with rituximab plus CHOP.—CH