San Diego, CA—Obinutuzumab (Gazyva)-based induction and maintenance chemotherapy extended progression-free survival (PFS) compared with standard-of-care rituximab (Rituxan)-based chemotherapy in patients with untreated follicular lymphoma, said Robert E. Marcus, MBBS, FRCP, FRCPath, King’s College Hospital, London, who presented the results from the phase 3 GALLIUM clinical trial at the 2016 American Society of Hematology meeting.
Obinutuzumab-based chemotherapy led to a 34% risk reduction for disease progression or death compared with rituximab-based chemotherapy, which was significant and clinically meaningful (P = .001), Dr Marcus said.
“For newly diagnosed patients with follicular lymphoma, obinutuzumab with chemotherapy is a better approach than with rituximab. Obinutuzumab-based chemotherapy significantly improved outcomes in this study, and should now be considered a first-line option for newly diagnosed patients with follicular lymphoma,” said Dr Marcus.
Approximately 30% of patients with follicular lymphoma had disease relapse within 3 years. Early relapse carries a poor prognosis and is challenging to treat, suggesting that maintenance therapy may have a role in improving outcomes.
The GALLIUM Clinical Trial
The multicenter GALLIUM clinical trial randomized 1202 patients with previously untreated follicular lymphoma in a 1:1 ratio to receive obinutuzumab-based or rituximab-based chemotherapy. Chemotherapy was physician’s choice of cyclophosphamide, vincristine, and prednisolone (10%); bendamustine (57%); or cyclophosphamide, doxorubicin, vincristine, and prednisone (33%). Patients with complete or partial response continued receiving their assigned anti-CD20 antibody for maintenance therapy every 8 weeks for 2 years.
“These patients all had poor prognosis and had aggressive disease. They all required treatment and were not a watch-and-wait population,” said Dr Marcus.
The overall response rate was approximately 85% in both treatment arms.
The study met the primary end point of investigator-assessed PFS by computed tomography scan criteria, with a 34% reduction in the risk for disease progression or death for obinutuzumab-based chemotherapy at a median follow-up of 34 months (P = .001). There were 101 patients with disease-progression events in the obinutuzumab arm versus 144 disease-progression events in the rituximab arm.
The median PFS had not been reached in either treatment arm, but the data suggest that the PFS will be approximately 1.5 times longer with obinutuzumab than with rituximab. At 3 years, 80% of patients who received obinutuzumab were disease-free compared with 73.3% of patients who received rituximab. All patients who received chemotherapy had a PFS benefit.
The time to next therapy was superior in the obinutuzumab arm compared with the rituximab arm; 87% of patients who received obinutuzumab were free from the need for therapy at 3 years.
Survival was similar between the 2 treatment arms.
Patients who received obinutuzumab had a higher incidence of febrile neutropenia, cytopenia, infections, and infusion-site reactions than patients who received rituximab. Non–lymphoma-related mortality was approximately 4% higher in the obinutuzumab group than in the rituximab group, mainly in patients who received bendamustine.
The higher incidence of adverse events associated with obinutuzumab therapy than with rituximab raises concerns about whether the PFS benefit outweighs the risks, especially because of the lack of an overall survival benefit. Not all patients will opt to receive 2 more years of maintenance therapy.
“Physicians should discuss these results with patients to decide whether the PFS benefits outweigh safety concerns,” Dr Marcus said.
Reactions to the study results were mixed, with some experts predicting that obinutuzumab induction and maintenance therapy will be a game-changer for patients with follicular lymphoma, whereas other experts urge caution because of the reported adverse events associated with obinutuzumab.
“This is a potentially practice-changing study that clearly shows an 8% absolute improvement in PFS at 2 years for the patients getting obinutuzumab versus rituximab. Obinutuzumab may get frontline indication for follicular lymphoma based on this study,” said Brad S. Kahl, MD, Medical Oncologist, Siteman Cancer Center, Washington University School of Medicine, St. Louis.
Olalekan Oluwole, MD, MBBS, MPH, Assistant Professor of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, cautioned that infection was a concern with bendamustine combinations. “It will be important for there to be awareness of this risk and take precautions when using bendamustine combinations,” Dr Oluwole said.
“In the absence of survival benefit, many patients will prefer an abbreviated program of treatment….It is the oncologist’s job to explain the pros and cons of treatment, and it is an individual decision for patients. If they prefer maintenance, then the study suggests obinutuzumab has a benefit,” said John P. Leonard, MD, Vice Chair of Clinical Research, Department of Medicine, Weill Cornell Medical College, New York, NY, who introduced Dr Marcus’s talk.