According to an exploratory analysis of the GALLIUM trial, obinutuzumab-based chemotherapy resulted in fewer incidences of disease progression compared to rituximab-based chemotherapy in previously untreated patients with advanced follicular lymphoma.
John F. Seymour, MBBS, PhD
According to an exploratory analysis of the GALLIUM trial, obinutuzumab (Gazyva)-based chemotherapy resulted in fewer incidences of disease progression compared to rituximab (Rituxan)-based chemotherapy in previously untreated patients with advanced follicular lymphoma.1
“Treatment with obinutuzumab-chemotherapy was associated with a marked reduction in the rate of [disease progression incidences after 24 months of randomization] relative to rituximab-chemotherapy,” concluded the investigators of the analysis. “These data therefore support the superiority of the obinutuzumab-chemotherapy regimen seen in the GALLIUM primary analysis.”
The international, phase III GALLIUM study included 1202 treatment-naïve patients with advanced-stage follicular lymphoma who were randomized to obinutuzumab plus chemotherapy, followed by obinutuzumab alone (n = 601), or rituximab plus chemotherapy, followed by rituximab alone (n = 601).2The chemotherapy regimens used were CHOP, CVP, or bendamustine, based on the discretion of the physicians at each study location.
At a median follow-up of 41.1 months, the study’s primary endpoint of progression-free survival by investigator assessment was significantly improved in those treated with obinutuzumab compared to rituximab (HR, 0.68; 95% CI, 0.54-0.87;P= .002). Based on these findings, obinutuzumab-based chemotherapy, followed by obinutuzumab alone, received an FDA approval in 2017 for the first-line treatment of patients with advanced follicular lymphoma.
The primary endpoint of the exploratory analysis was disease progression or death due to disease progression within 24 months of randomization in the study. Secondary measures included overall survival (OS) and mortality after 6, 12, 18, and 24 months of randomization in patients with or without progression after 24 months.
Of the 1071 patients eligible for evaluation, cumulative incidences of early disease progression occurred in 10.1% (95% CI, 8-12%) of patients treated with obinutuzumab (57/601) versus 17.4% (95% CI, 14-20%) of patients treated with rituximab (98/601), while the average hazard ratio (HR)-based reduction in risk of an incident occurring with obinutuzumab relative to rituximab of 46.0% (95% CI, 25.0-61.1%;P= 0.0003). The data cutoff for this analysis was September 10, 2016 with a median follow-up of 41 months.
“Fewer [incidences] occurred in obinutuzumab-chemotherapy versus rituximab-chemotherapy patients across all 3 chemotherapy regimen groups,” added the investigators. The highest rate of events was observed in those patients treated with CVP.
The investigators of the exploratory analysis, however, sited notable differences between patients who did and did not experience incidences of disease progression. The patients who had events of disease progression after 24 months were more likely to have specified features including male, stage IV disease, grade IIIa histology, high FLIPI risk, elevated serum lactate dehydrogenase, and bulky disease.
Fifty-six of the 155 patients who experienced disease progression after 24 months of randomization among both cohorts of the study died. A total of 40 patients died due to disease progression (obinutuzumab-based chemotherapy, n = 15; rituximab-based chemotherapy, n = 25) and 16 for other reasons (n = 4 and n = 12, respectively) not specified in the analysis.
For patients (n = 916) who did not progress after 24 months on either immunochemotherapy regimen, 1 patient died due to disease progression who did not receive treatment from the study and 15 patients died for other unstated reasons (obinutuzumab-based chemotherapy, n = 9; rituximab-based chemotherapy, n = 6).
The 2-year OS rate for patients still alive at 24 months was 82.4% (95% CI, 74.2-91.3%) for those who experienced progression of disease and 98.2% (95% CI, 97.1-99.2%) for patients who did not.
“With small numbers of deaths in both arms and comparatively short follow-up, it should be noted that, despite a reduced risk of [patients who progressed] with obinutuzumab-chemotherapy, we have not seen an impact on OS in the GALLIUM study,” said the investigators. “However, this is not unexpected with current follow-up given available salvage therapies.