GALLIUM Findings Support Obinutuzumab For Advanced Follicular Lymphoma

Replacing rituximab-based treatment with an obinutuzumab-based regimen extends progression-free survival for treatment-naive patients with advanced follicular lymphoma

medwireNews: Patients undergoing first-line treatment for advanced follicular lymphoma derive greater benefit from induction and maintenance chemotherapy including obinutuzumab than from a rituximab-based regimen, indicate phase III study findings published in The New England Journal of Medicine.

“[T]he results of this large collaborative trial show that the replacement of rituximab with obinutuzumab in the context of immunochemotherapy and maintenance therapy in patients with previously untreated follicular lymphoma resulted in significantly longer progression-free survival [PFS]”, say the GALLIUM investigators.

Patients were randomly assigned to receive induction obinutuzumab 1000 mg on day 1, 8 and 15 of cycle 1 followed by a dose on day 1 of the following six or eight cycles, depending on the accompanying chemotherapy regimen, or to receive rituximab 375 mg/m2 on day 1 of each of six or eight cycles.

Patients who achieved a complete or partial response then continued with the same anti-CD20 agent dose given every 2 months for 2 years or until disease progression or withdrawal, explain Robert Marcus, from King’s College Hospital, London, UK, and co-authors.

They report that the obinutuzumab and rituximab treatment arms achieved similar rates of both complete or partial response (88.5 vs 86.9%) and complete response (19.5 vs 23.8%) by the end of induction therapy.

But planned interim analysis after a median of 34.5 months demonstrated significantly longer PFS for the 601 patients given obinutuzumab compared with the 601 patients who were treated with rituximab, with 3-year estimated rates of 80.0% versus 73.3% and a hazard ratio for progression, relapse or death of 0.66.

In all, 5.8% of patients died in the obinutuzumab arm and 7.7% in the rituximab-treated patient group, giving comparable estimated 3-year overall survival rates of 94.0% versus 92.1%.

Obinutuzumab was associated with a higher rate of grade 3–5 side effects (74.6 vs 67.8%) and serious adverse events (46.1 vs 39.9%) than rituximab, including fatal events (4.0 vs 3.4%). Infusion-related events were the most common adverse event reported, with any-grade events affecting 59.3% and 48.9% of patients, respectively, followed by nausea (46.9 and 46.6%) and neutropenia (48.6 and 43.6%).

Robert Marcus and the GALLIUM co-investigators admit that the trial findings may be subject to confounding as the study was not designed to compare the efficacy or safety of the bendamustine, CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) and CVP (cyclophosphamide, vincristine and prednisone) chemotherapy regimens accompanying the anti-CD20 agents.

However, they suggest: “Recent data regarding the rates of molecular complete response in our trial suggest that less-intensive chemotherapy regimens given with obinutuzumab still have greater efficacy than when they are given with rituximab, and they might be of value in frailer patients, for whom bendamustine or CHOP would be less suitable, while maintaining the overall beneficial effect of obinutuzumab.”

Reference

Marcus R, Davies A, Ando K, et al. Obintuzumab for the first-line treatment of follicular lymphoma. N Engl J Med 2017; 377: 1331–1344. 5 October 2017. DOI: 10.1056/NEJMoa1614598

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