The FDA has approved obinutuzumab (Gazyva) in combination with chemotherapy, followed by obinutuzumab alone, for the first-line treatment of patients with advanced follicular lymphoma, according to Genentech, the manufacturer of the therapy.
The approval which is for patients with stage II bulky, III or IV disease, is based on data from the phase III GALLIUM study, in which combining obinutuzumab with chemotherapy in the first-line setting reduced the risk of disease progression or death by 28% versus rituximab plus chemotherapy in patients with follicular lymphoma (HR, 0.72; 95% CI, 0.56-0.93; P = .0118).
“Today’s Gazyva approval is an important advance for the thousands of people diagnosed each year with follicular lymphoma who hope to delay disease progression for as long as possible,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a press release. “We’re pleased we can now offer patients with this incurable blood cancer an initial treatment option shown to improve upon Rituxan, the standard of care in this setting for more than 10 years.”
The international phase III GALLIUM study included 1401 treatment-naive patients with indolent non-Hodgkin lymphoma, of whom 1202 had follicular lymphoma. Patients with follicular lymphoma were aged ≥18 years, had grade I to Iliac disease, and an ECOG performance status ≤2.
Patients were randomized to obinutuzumab plus chemotherapy, followed by obinutuzumab alone (n = 601), or rituximab plus chemotherapy, followed by rituximab alone (n = 601). The chemotherapy regimens used were CHOP, CVP, or bendamustine, based on the discretion of the physicians at each study location.
Patients specifically received rituximab at 375mg/m2 on day 1 of each cycle or obinutuzumab at 1000 mg on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles, for either eight 21-day cycles (CHOP and CVP) or six 28-day cycles (bendamustine). Among patients randomized to chemotherapy, 57.1%, 33.1%, and 9.8%, received bendamustine, CHOP, and CVP, respectively.
The primary endpoint of the study was progression-free survival (PFS). Secondary outcome measures included response rate, overall survival, disease-free survival, and safety. The study was unblinded per the recommendation of an independent data monitoring panel in January 2016 after a preplanned interim efficacy analysis.
At a median follow-up of 41.1 months, the hazard ratio (HR) for PFS by investigator assessment was 0.68 (95% CI, 0.54-0.87; P= .0016). Per independent review, the HR for PFS was 0.72 (95% CI, 0.56-0.93; P = .0018). The median PFS has not been reached yet in either treatment arm.
The overall response rate was 91% in the obinutuzumab arm and 88% in the control arm. Complete remission rates were 28% and 27%, respectively.
Safety data from the 41.1-month follow-up showed that the most common grade 3/5 adverse events that occurred more often in the obinutuzumab arm compared to the rituximab arm were neutropenia (46.7% vs 39.5%), infections (20.3% vs 16.4%), infusion-related reactions (12.4% vs 6.7%), thrombocytopenia (6.1% vs 2.7%), second malignancies (4.7% vs 2.7%), and cardiac events (3.9% vs 2.8%).
Obinutuzumab is a glycoengineered antibody against CD20. Through the glycoengineering process, sugar molecules are removed from immune-effector antibody cells in the posttranslational setting, significantly impacting antigen binding and function. Specifically, obinutuzumab is designed to lack fucose molecules.
The FDA previously approved obinutuzumab for use in combination with bendamustine for patients with follicular lymphoma who have received prior therapy.