By Reuters Staff
NEW YORK (Reuters Health) - Obinutuzumab combined with bendamustine is more effective than bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma, according to results from the phase 3 GADOLIN trial.
Bendamustine monotherapy has been associated with 75-80% response rates in patients with refractory indolent non-Hodgkin lymphoma, but the benefits are short-lived. Obinutuzumab, an anti-CD20 monoclonal antibody, has shown encouraging activity in patients like these.
Dr. Laurie H. Sehn, from the University of British Columbia, Vancouver, Canada, and colleagues in the GADOLIN trial assessed the efficacy and safety of induction therapy with obinutuzumab and bendamustine followed by obinutuzumab maintenance therapy, compared with bendamustine monotherapy as induction therapy, in an open label, randomized, phase 3 study of 396 patients with rituximab-refractory indolent non-Hodgkin lymphoma.
Enrollment was terminated early after a protocol-specified interim efficacy analysis found progression-free survival to be significantly improved in the obinutuzumab arm of the study.
About 80% of patients in both treatment groups received 90% or more of the total bendamustine dose in the induction phase. However, 16% of patients in the obinutuzumab group and 28% of patients in the bendamustine monotherapy group withdrew from induction therapy before receiving all scheduled doses. Moreover, 18% of obinutuzumab patients and 27% of bendamustine monotherapy patients required at least one bendamustine dose reduction.
At the time of analysis, progression-free survival events had occurred in 71 (37%) patients in the obinutuzumab plus bendamustine group and 104 (51%) patients in the bendamustine monotherapy group, according to the June 23 Lancet Oncology online report.
After a median follow-up time of 21.9 months, median progression-free survival had not been reached in the obinutuzumab group. In the bendamustine monotherapy group, however, median progression-free survival was 14.9 months after a median follow-up of 20.3 months (p=0.0001).
The two treatment groups did not differ in end-of-induction overall response or best overall response. Although patients in the obinutuzumab group fared better in most of the secondary endpoints, there was no significant difference in overall survival between the treatment groups.
Most patients experienced at least one adverse event during the course of the study. Three of 12 deaths due to adverse events in the obinutuzumab group and five of 12 deaths due to adverse events in the bendamustine monotherapy group were deemed treatment related.
"The addition of obinutuzumab to bendamustine followed by obinutuzumab maintenance resulted in a clinically meaningful and significant improvement in progression-free survival compared with bendamustine monotherapy, with a manageable toxicity profile," the researchers conclude. "Indeed, the hazard ratio (HR) is comparable to the benefit previously shown with the addition of rituximab to chemotherapy in rituximab-naive patients."
F Hoffmann-La Roche funded the trial. All but two of the 17 authors had various relationships with Roche/Genentech, including three authors who were employed by Roche.
Dr. Sehn did not respond to a request for comments.
Lancet Oncol 2016.
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