Obinutuzumab Could Be ‘New Standard Of Care’ In Previously Untreated Follicular Lymphoma

Improved progression-free survival with obinutuzumab- versus rituximab-based therapy in patients newly diagnosed with follicular lymphoma

medwireNews: Data from the phase III GALLIUM trial support the use of obinutuzumab-based induction and maintenance therapy rather than a rituximab-based regimen in treatment-naive follicular lymphoma patients.

These results, comparing the two anti-CD20 antibodies, were presented by Robert Marcus, from Kings College Hospital in London, UK, at the annual meeting of the American Society of Hematology, held in San Diego, California, USA.

A total of 1202 patients with untreated follicular lymphoma were randomly assigned to receive either obinutuzumab 1000 mg on days 1, 8 and 15 of the first cycle and day 1 of subsequent cycles or rituximab 375 mg/m2 on the first day of each cycle. Patients also received concurrent chemotherapy, either bendamustine, CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CVP (cyclophosphamide, vincristine and prednisone) at the investigators’ discretion. Individuals who responded to the induction regimen continued to receive the same antibody every 2 months for 2 years or until disease progression.

The presenter reported that the primary endpoint of investigator-assessed progression-free survival (PFS) was achieved by a higher proportion of the 601 patients given the obinutuzumab-based regimen than the 601 who received rituximab-based therapy, with 3-year PFS rates of 80.0% versus 73.3%, equating to a significant hazard ratio (HR) of 0.66.

The significant difference between groups was maintained when PFS was assessed by an independent review committee, with 81.9% and 77.9% of patients in the obinutuzumab and rituximab groups, respectively, remaining progression-free at 3 years (HR=0.71).

Moreover, obinutuzumab-treated participants were a significant 32% less likely than those given rituximab to receive further anti-lymphoma therapy.

But the proportion of patients achieving an objective response – as assessed by computed tomography – did not differ significantly between the study arms. In response to an audience member querying this lack of difference, Robert Marcus pointed out that computer tomography-based remissions are “unreliable” in this setting and they await the results of the positron emission tomography analysis.

He also discussed the safety data, which showed that patients in the obinutuzumab group were more likely than their rituximab-treated counterparts to experience grade 3 or more severe febrile neutropenia (6.9 vs 4.9%), infections (20.0 vs 15.6%) and infusion-related reactions (12.4 vs 6.7%).

Of note, the incidence of grade 5 – that is, fatal – events was “somewhat higher” than expected in both the obinutuzumab and rituximab groups, with comparable mortality rates of 4.0% and 3.4%, respectively, said the presenter.

This increase seemed largely attributable to bendamustine, as the overall mortality rate was higher for these patients (around 5% for the obinutuzumab and rituximab groups) than for those given CHOP or CVP (around 2% in either group). But a post hoc analysis showed that all patients derived a PFS benefit regardless of the chemotherapy regimen, and “individual clinicians will have to decide whether any PFS benefits associated with more intensive regimens outweigh any safety concerns”, he remarked.

Robert Marcus concluded that their findings support obinutuzumab-based therapy becoming a new first-line standard of care for follicular lymphoma patients.

Reference

Marcus RE, Davies AJ, Ando K, et al. Obinutuzumab-based induction and maintenance prolongs progression-free survival (PFS) in patients with previously untreated follicular lymphoma: primary results of the randomized phase 3 GALLIUM study. ASH Annual Meeting 2016; San Diego, California, USA: 3–6 December.

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