Induction and maintenance therapies with obinutuzumab (Gazyva) were superior to rituximab (Rituxan) induction and maintenance in patients with untreated follicular lymphoma, according to results of the phase III GALLIUM study presented at the Plenary Session during the 58th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego.1
Obinutuzumab-based chemotherapy achieved a statistically significant and clinically meaningful 34% reduction in the risk of progression or death vs rituximab-based chemotherapy (P = .001).
Obinutuzumab-based chemotherapy significantly improved outcomes in this study and should now be considered an option for newly diagnosed follicular lymphoma patients.— Robert Marcus, MD
“For newly diagnosed follicular lymphoma patients, obinutuzumab with chemotherapy is a better approach than rituximab with chemotherapy. Obinutuzumab-based chemotherapy significantly improved outcomes in this study and should now be considered an option for newly diagnosed follicular lymphoma patients,” said Robert Marcus, MD, of Kings College Hospital, London, who presented these results at the ASH meeting.
“About 30% of patients will relapse within 3 years and have a poor prognosis. It is challenging to treat relapse, especially early relapse, in follicular lymphoma patients,” Dr. Marcus told listeners.
GALLIUM was designed to compare the efficacy and safety of two anti-CD20 monoclonal antibodies—rituximab and obinutuzumab—in patients with previously untreated indolent non-Hodgkin lymphoma. The results Dr. Marcus presented pertained to a cohort of patients with follicular lymphoma, all of whom required therapy.
The study randomly assigned 1,202 patients 1:1 to either obinutuzumab-based chemotherapy or rituximab-based chemotherapy. Since there is no consensus on first-line chemotherapy for follicular lymphoma, individual physicians could choose among CVP (cyclophosphamide, vincristine, prednisone), bendamustine, or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
Bendamustine was the most commonly used chemotherapy (57% of patients); CHOP was used in about one-third of patients, and the rest received CVP. Responding patients (either a complete or partial response) remained on the same CD20 antibody given every 8 weeks for 2 years of maintenance therapy.
At baseline, more than 40% of patients in both arms had a poor prognosis (ie, high Follicular Lymphoma International Prognostic Index score). Forty-five percent had bulky disease, and 60% had extranodal involvement.
“These were all poor-prognosis patients with aggressive disease. They were not a watch-and-wait population,” Dr. Marcus said.
The overall response rate was 85% in both arms. About 50% of patients had positron-emission tomography scans at the end of induction therapy, and results will be analyzed in the future.
The study met the primary endpoint of investigator-assessed progression-free survival by computed tomography scan criteria, with a 34% reduction in the risk of progression or death for obinutuzumab-based chemotherapy vs rituximab-based chemotherapy at a median follow-up of 34 months (P = .001). Median progression-free survival has not been reached in either arm, but the data suggest that progression-free survival will be about 1.5 times longer with obinutuzumab than with rituximab. About 81% of patients were disease-free at 3 years in the obinutuzumab arm.
“Time to next therapy was superior in the obinutuzumab-treatment arm. Eighty-seven percent of patients in the obinutuzumab arm remained free of the need for therapy at 3 years,” Dr. Marcus said.
There was no difference in overall survival between the two arms.
A detailed safety analysis raised some concerns. There was an increased incidence of febrile neutropenia, cytopenias, infections, and infusion-site reactions in patients who received obinutuzumab-based chemotherapy compared with rituximab-based chemotherapy. A higher incidence of fatal adverse events and about a 4% higher nonlymphoma mortality was observed in the obinutuzumab group, predominantly in patients receiving bendamustine. A small incidence of secondary malignancies was seen in both arms.
“The level of mortality in both arms was higher than we might expect with induction therapy for follicular lymphoma,” Dr. Marcus said.
“Individual clinicians will have to make that decision about whether the progression-free survival benefits outweigh safety concerns,” he told listeners. ■
Disclosure: The study was supported by Roche. Dr. Marcus reported serving as a consultant for and receiving honoraria from Roche and receiving travel support from Takeda.
1. Marcus RE, Davies AJ, Ando K, et al: Obinutuzumab-based induction and maintenance prolongs progression-free survival in patients with previously untreated follicular lymphoma: Primary results of the randomized phase 3 GALLIUM study. 2016 ASH Annual Meeting. Abstract 6. Presented December 4, 2016.