Obinutuzumab Plus Bendamustine Adds To Treatment-Refractory Indolent NHL Armamentarium

Obinutuzumab plus bendamustine may set new standard for rituximab-refractory indolent CD20-positive non-Hodgkin lymphoma

medwireNews: The addition of obinutuzumab to bendamustine therapy improves progression-free survival (PFS) in patients whose indolent CD20-positive non-Hodgkin lymphoma (NHL) is refractory to rituximab therapy, the GADOLIN investigators say.

They believe that their study published in The Lancet Oncology is the “first to show that an alternative anti-CD20 monoclonal antibody is clinically useful for patients with rituximab-refractory indolent non-Hodgkin lymphoma who are no longer benefiting from rituximab.”

Enrolment to the open-label phase III trial was halted at the pre-planned interim analysis after the primary endpoint of a 30% reduction in the risk of progression with obinutuzumab treatment was achieved, with a significant hazard ratio of 0.55, write Laurie Sehn, from British Columbia Cancer Agency in Vancouver, Canada, and co-authors.

After a median of 21.9 months of follow-up, median PFS had not been reached in the 194 patients randomly assigned to receive six 28-day cycles of obinutuzumab plus bendamustine therapy followed by maintenance obinutuzumab therapy for up to 2 years. By contrast, the 202 patients given bendamustine monotherapy had a median PFS of 14.9 months.

The GADOLIN investigators say that the obinutuzumab plus bendamustine regimen had a “manageable toxicity profile”.

Grade 3 or more severe adverse events in patients given both agents included neutropenia (33%), thrombocytopenia (11%), infusion-related reactions (11%) and anaemia (8%). Serious events occurred in 38% of the combined therapy group versus 33% of the monotherapy group, with three and five treatment-related deaths, respectively.

Paul Hamlin, from Memorial Sloan Kettering Cancer Center in New York, USA, notes in an accompanying comment that as indolent NHL patients are now frequently given rituximab plus bendamustine as a first-line regimen, the current study’s relevance is “unclear” to those previously exposed to bendamustine.

He also observes that minimal residual disease status at end of induction therapy might be a “powerful biomarker” for identifying which patients should continue with maintenance therapy, noting that patients who remained positive for minimal disease did not benefit from further treatment.

“Ultimately, obinutuzumab plus bendamustine followed by 2 years of maintenance obinutuzumab represents an attractive option for rituximab refractory patients, supporting a 2016 [US Food and Drug Administration] indication for [obinutuzumab] based on these data, and establishing a new standard in this setting”, Paul Hamlin concludes.


Sehn LH, Chua N, Mayer J, et al. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol 2016; Advance online publication 23 June. DOI:

Hamlin PA. Obinutuzumab plus bendamustine in rituximab-refractory indolent lymphoma. Lancet Oncol 2016; Advance online publication 23 June. DOI:

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