Obinutuzumab and Early Progression of Patients with Previously Untreated Follicular Lymphoma − Analysis of Data from the GALLIUM Study

Obinutuzumab and the GALLIUM Study

Obinutuzumab is a recombinant humanized type II monoclonal antibody against the CD20 antigen on the surface of B lymphocytes. Compared to type I anti-CD20 antibodies (e.g., rituximab), obinutuzumab is characterized by increased induction of direct cell death and decreased complement-dependent cytotoxicity.  

The GALLIUM study was a clinical trial comparing the impact of rituximab and obinutuzumab-based therapy on PFS in patients with previously untreated stage I−IIIa FL. Patients enrolled in the study were randomized on a 1:1 basis. The first group received rituximab and chemotherapy (CHOP regimen, i.e., cyclophosphamide, doxorubicin, vincristine, prednisone; or CVP, i.e., cyclophosphamide, vincristine, prednisone; or bendamustine), while the second group received obinutuzumab in combination with chemotherapy in 6−8 cycles depending on the specific regimen. Patients who responded to the combination treatment with anti-CD20 antibody and chemotherapy continued with anti-CD20 antibody treatment for the next 2 years.

Exploratory Data Analysis

The goal of the recently published analysis of data from the GALLIUM study was to evaluate the impact of targeted therapy on early disease progression and the relationship between early progression and OS. The primary evaluated parameter of this analysis was progression or death due to disease progression within 24 months from randomization. Patient mortality was assessed at intervals of 6, 12, 18, and 24 months from randomization. The risk of early progression or death due to early progression was evaluated using the Cox regression model.

Findings

In the group treated with obinutuzumab-based immunochemotherapy, disease progression occurred in 57 out of 601 patients. In the group treated with rituximab-based immunochemotherapy, 98 out of 601 patients experienced progression. The mean reduction in the risk of disease progression in the first 24 months with obinutuzumab treatment thus reached 46.0% (95% confidence interval [CI] 25.0−61.1%; cumulative incidence 10.1 vs. 17.4%). Time-dependent regression analysis demonstrated that disease progression within 24 months from the start of treatment was associated with significantly higher mortality at any point during follow-up (stratified hazard ratio [HR] 25.5; 95% CI 16.2−40.3). The earlier the disease progression occurred, the worse the patient's prognosis.

Conclusion

Obinutuzumab-based immunochemotherapy significantly reduced the risk of early disease progression in patients with previously untreated FL compared to rituximab-based treatment. Early progression is associated with higher mortality and a worse overall prognosis for patients.

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Source: Seymour J. F., Marcus R., Davies A. et al. Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression. Haematologica 2019; 104 (6): 1202−1208, doi: 10.3324/haematol.2018.209015.