According to results from the phase III GALLIUM study, patients with previously untreated follicular lymphoma (FL) may benefit from frontline therapy with obinutuzumab, a humanized anti-CD20 monoclonal antibody, according lead author Robert E. Marcus, MBBS, from King’s College Hospital in London.
“At this interim efficacy analysis, obinutuzumab plus chemotherapy and maintenance [therapy] is superior to rituximab plus chemotherapy and maintenance [therapy] in untreated advanced FL,” said Dr. Marcus, noting the “clinically meaningful” improvement in progression-free survival (PFS). “What this may lead to, which is subject to the survival curves remaining stable, will be an improvement in PFS in first remission of over eight years.”
The multicenter, randomized, open-label trial compared the efficacy and safety of rituximab or obinutuzumab with chemotherapy, followed by maintenance therapy, in 1,401 adult patients with indolent non-Hodgkin lymphoma: 1,202 patients had previously untreated FL (grades 1-3a) and 199 had chemotherapy-naïve marginal zone lymphoma (MZL).
Patients were randomized to receive chemotherapy plus either rituximab (n=601; 375 mg/m2 on day 1 of each cycle) or obinutuzumab (n=601; 1,000 mg on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles), for six to eight treatment cycles. Patients who achieved a complete response (CR) or partial response (PR) at the end of induction therapy then received maintenance therapy with rituximab or obinutuzumab every two months for two years or until disease progression.
The overall response rate (ORR) was slightly higher in the obinutuzumab group than in the rituximab group (88.5% vs. 86.9%), with slightly more patients experiencing CR with rituximab treatment (p values not provided):
- CR rates: 23.8% vs. 19.5%
- PR rates: 69.1% vs. 63.1%
After a median follow-up of 34.5 months, the three-year PFS rate was 80 percent in the obinutuzumab arm, compared with 73.3 percent in the rituximab arm, for a 34 percent reduction in the risk of disease progression or death (hazard ratio [HR] = 0.66; 95% CI 0.51-0.85; p=0.0012).
Obinutuzumab treatment was also associated with a non-significant 25-percent lower risk of death: Rates of three-year overall survival (OS; a secondary endpoint) were 94 percent in the obinutuzumab group and 92.1 percent in the rituximab group (HR=0.75; 95% CI 0.49-1.17; p=0.21).
Obinutuzumab-treated patients had a higher frequency of grade 3-5 adverse events (AEs) and serious AEs (74.6% and 46.1%, respectively; p values not provided) compared with rituximab-treated patients (67.8% and 39.9%, respectively; p values not provided).
“Obinutuzumab-based regimens should now be considered one of the options for firstline therapy for patients with follicular lymphoma,” Dr. Marcus concluded. However, given the higher AE rates with obinutuzumab, he advised that “individual clinicians will have to make the decision as to whether any benefits in PFS with more intensive regimens outweigh any safety concerns.”
Limitations of the study include the lack of a demonstrated survival benefit, whether a survival benefit would extend to patients not receiving maintenance therapy, or whether the choice of chemotherapy affects response.
Marcus RE, Davies AJ, Ando K, et al. Obinutuzumab-based induction and maintenance prolongs progression-free survival (PFS) in patients with previously untreated follicular lymphoma: primary results of the randomized phase 3 GALLIUM study. Abstract #6. Presented at the 2016 ASH Annual Meeting, December 4, 2016; San Diego, California.