Some patients with follicular lymphoma (FL) have a poor prognosis, with about 30 percent of patients relapsing within three years. According to results from the phase III GALLIUM study, patients with previously untreated FL may benefit from frontline therapy with obinutuzumab, a humanized anti-CD20 monoclonal antibody, according to Robert E. Marcus, MBBS, who reported results from this study during the Plenary Abstract Session at the 2016 ASH Annual Meeting.
“At this interim efficacy analysis, obinutuzumab plus chemotherapy and maintenance [therapy] is superior to rituximab plus chemotherapy and maintenance [therapy] in untreated advanced follicular lymphoma,” Dr. Marcus said, 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 progression-free survival in first remission of over eight years.”
The multicenter, randomized, open-label GALLIUM 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 treated with either bendamustine (57.1%), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; 33.1%), or CVP (cyclophosphamide, vincristine, and prednisone; 9.8%) and randomized 1:1 to receive chemotherapy plus either rituximab (n=601) or obinutuzumab (n=601). Therapy consisted of 375 mg/m2 of rituximab on day 1 of each cycle or 1000 mg of obinutuzumab on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles, for either eight 21-day cycles (CHOP- and CVP-treated patients) or six 28-day cycles (bendamustine-treated patients).
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), per investigator assessment. According to Dr. Marcus and co-authors, this translates to “a 1.5-times longer median PFS for obinutuzumab plus chemotherapy than rituximab plus chemotherapy, and to an estimated three-year improvement in the obinutuzumab arm if a median PFS of six years was assumed in the rituximab arm.”
An Independent Review Committee found similar results: The three-year PFS rate was 81.9 percent in the obinutuzumab arm and 77.9 percent in the rituximab arm, for a 29-percent reduction in the risk of disease progression or death (HR=0.71; 95% CI 0.54-0.93; p=0.0138).
Ninety-two percent of patients in the obinutuzumab arm achieved minimal-residual disease negativity in blood and/or bone marrow, compared with 84.9 percent in the rituximab arm (p=0.0041).
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 94.0 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 AEs and serious AEs (74.6% and 46.1%, respectively; p values not provided) compared with rituximab-treated patients (67.8% and 39.9%; p values not provided). The frequency of fatal AEs was similar in both groups (4.0% and 3.4%), as was the rate of AEs that led to treatment discontinuation (16.3% and 14.2%).
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.
“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 progression-free survival with more intensive regimens outweigh any safety concerns.”
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.