This article is more than 5 years old. Information may no longer be current.
Obinutuzumab plus bendamustine prolongs PFS in rituximab-refractory non-Hodgkin lymphoma
The addition of obinutuzumab to bendamustine followed by obinutuzumab maintenance therapy improved PFS among patients with rituximab-refractory non-Hodgkin lymphoma, according to the results of a multicenter phase 3 trial.
“Patients who fail to respond to a rituximab [Rituxan, Genentech/Biogen]-containing regimen have few treatment options and a poor prognosis,” Laurie H. Sehn, MD, MPH, clinical associate professor at University of British Columbia in Vancouver, Canada, and colleagues wrote. “Bendamustine [Treanda, Cephalon] given as monotherapy has seen 75% to 80% of patients achieving a response in this setting, but the benefit is short-lived, with a median PFS of 7 to 9 months.”
Laurie H. Sehn
Sehn and colleagues evaluated whether the addition of the glyco-engineered type II anti-CD20 monoclonal antibody obinutuzumab (Gazyva, Genentech) to standard therapy with bendamustine would improve outcomes in 396 patients (median age, 63 years).
Researchers used a hierarchical dynamic randomization scheme — stratified by disease subtype, rituximab-refractory type, number of previous therapies and geographical region — to randomly assigned patients 1:1 to receive bendamustine alone (n = 202) or with obinutuzumab (n = 194).
Patients in the obinutuzumab plus bendamustine arm received 1,000 mg IV obinutuzumab on days 1, 8 and 15 in cycle 1 and on day 1 for cycles 2 through 6, along with 90 mg/m2 IV bendamustine on days 1 and 2 of cycles 1 through 6. Patients who did not experience progression received 1,000 mg maintenance obinutuzumab every 2 months for up to 2 years.
Patients in the bendamustine monotherapy arm received 120 mg/m2 IV bendamustine on days 1 and 2 of all cycles.
PFS served as the primary endpoint.
Median follow-up was 21.9 months in the obinutuzumab arm and 20.3 months in the control arm.
PFS appeared significantly longer among patients in the obinutuzumab arm (median not reached vs. 14.9 months; HR = 0.55; 95% CI, 0.4-0.74).
The combination appeared well tolerated, even though patients had a longer treatment duration.
Grade 3 to grade 5 adverse events occurred in 62% of patients in the obinutuzumab group and 68% of patients in the control group. The most common grade 3 or worse adverse events included neutropenia (obinutuzumab, 33%; control, 26%), thrombocytopenia (11% vs. 16%), anemia (8% vs. 10%) and infusion-related reactions (11% vs. 6%).
Serious adverse events occurred in 38% of patients in the obinutuzumab group and 33% in the control group. Twelve patients from each group died of an adverse event, some of which were treatment related (obinutuzumab, n = 3; control, n = 5).
“The addition of obinutuzumab to bendamustine followed by obinutuzumab maintenance resulted in a clinically meaningful and significant improvement in PFS compared with bendamustine monotherapy, with a manageable toxicity profile,” Sehn and colleagues wrote.
Although these data appear to offer an attractive option for patients with rituximab-refractory disease, additional research is necessary, Paul H. Hamlin, MD, medical oncologist and chief of the Basking Ridge Medical Oncology Service, wrote in an accompanying editorial.
“A number of open questions remain for further investigation,” he wrote. “In the current environment, bendamustine plus rituximab is increasingly a first-line regimen and the relevance of this study is unclear in patients previously exposed to bendamustine. ... About 30% of patients seem to be refractory to both obinutuzumab plus bendamustine and bendamustine therapy at induction; characterizing this group of patients and offering alternative approaches should be the focus of future research.” – by Nick Andrews
Disclosure: Sehn reports consultant fees and research funding from AbbVie, Amgen, Celgene, Gilead, Janssen, Lundbeck, Pfizer, Roche/Genentech, Seattle Genetics and TG Therapeutics. Hamlin reports advisory board roles with and research support from Celgene, Gilead, Molecular Templates, Novartis, Portola, Roche/Genentech, Seattle Genetics and Spectrum. Please see the full study for a list of all other researchers' relevant financial disclosures.