Prolonged PFS With Obinutuzumab in Advanced FL, Regardless of Chemo Backbone

June 25, 2018

AEs were more common in patients assigned to obinutuzumab compared with rituximab; however, baseline characteristics differed between treatment arms.

Treatment with obinutuzumab significantly prolonged progression-free survival (PFS) in patients with previously untreated follicular lymphoma (FL) compared with rituximab (R), regardless of the chemotherapy backbone with which it was combined, according to results of the GALLIUM study, published in the Journal of Clinical Oncology.

The current data build on previous findings from GALLIUM, which showed a significant improvement with obinutuzumab (also known as GA101, and designated as G in the study) in patients treated with either CHOP (a regimen comprising cyclophosphamide, doxorubicin, vincristine, and prednisone) , CVP (cyclophosphamide, vincristine, and prednisone), or bendamustine.

“Although GALLIUM was not designed to detect significant differences between antibody arms at the chemotherapy backbone level, and such a comparison is confounded by imbalances in baseline characteristics due to the nonrandomized selection of chemotherapy, our results demonstrate that the efficacy benefits of G persisted with all three chemotherapy backbones,” wrote Wolfgang Hiddemann, MD, University Hospital, Munich, Germany, and colleagues.

The study included 1,202 patients with treatment-naive advanced disease. Patients were randomly assigned to obinutuzumab at 1,000 mg (on days 1, 8, and 15 of cycle 1 and on day 1 of subsequent cycles) or rituximab at 375 mg/m2 (on day 1 of each cycle, for 6 to 8 cycles) combined with a chemotherapy regimen allocated nonrandomly by the treating center. Patients who responded could receive either drug for 2 years or until disease progression.

Baseline characteristics differed by chemotherapy regimen. Comorbidities were more common in the bendamustine group, and fewer patients assigned to CHOP were over 80 years of age, compared with the other two groups.

After a median follow-up of about 3.5 years, PFS was significantly longer in all patients assigned to obinutuzumab, regardless of the assigned chemotherapy arm. The hazard ratio for investigator-assessed PFS was 0.63 for bendamustine, 0.72 for CHOP, and 0.79 for CVP. The three-year PFS rates were also higher for patients assigned to obinutuzumab rather than rituximab.

Adverse events varied by chemotherapy arm and were more common in patients assigned to obinutuzumab compared with rituximab. Grade 3 to 5 adverse events, specifically cytopenias, occurred most frequently in patients assigned to treatment with CHOP.

Grade 3 to 5 infections, second neoplasms, and fatal events occurred most frequently in patients assigned to bendamustine.

“A possible explanation for this finding may be the substantial and long-lasting suppression of CD3+ and CD3+ CD4+ T cells in the bendamustine group,” the researchers wrote. “Similar findings were reported in heavily pretreated patients with indolent lymphomas who received R plus bendamustine.”

They also noted that the increase in fatal events seen with bendamustine was likely confounded by age and by comorbidity differences in baseline characteristics.

In light of their results, Hiddemann et al emphasized that “the most appropriate chemotherapy partner should be selected with care, taking individual patient characteristics and risk profiles into consideration.”