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The combination of obinutuzumab plus chemotherapy delivered superior long-term progression-free survival benefit for patients with treatment-naïve follicular lymphoma.
The combination of obinutuzumab (Gazyva) plus chemotherapy delivered superior long-term progression-free survival (PFS) benefit for patients with treatment-naïve follicular lymphoma (FL), according to final analysis of the phase 3 GALLIUM trial (NCT01332968).1
At median follow-up of 7.9 years, the 7-year PFS for patients who received obinutuzumab/chemotherapy was 63.4% compared with 55.7% for patients who received rituximab (Rituxan) plus chemotherapy (HR, 0.77; 95% CI, 0.64-0.93; P = .006).
“Meaningful improvement in PFS has been maintained with obinutuzumab/chemotherapy, with a 23% reduction in the risk of PFS and hazard ratio of .77, translating also into longer time to next treatment,” lead author William Townsend, MD, a consultant hematologist at University College London Hospitals, said at the 2022 EHA Congress. “This confirms again that the GALLIUM trial represents another step forward in the treatment of previously untreated advanced stage follicular lymphoma. This is one of the largest trials assessing the value of end of induction PET [positron emission tomography-computed tomography], and this long term data confirms the predictive value of that for both PFS and overall survival.”
In GALLIUM, investigators randomly assigned 1202 patients with previously untreated FL to induction therapy with obinutuzumab/chemotherapy (n = 601) or rituximab/chemotherapy (n = 601). Patients then received 2 years of maintenance therapy with the same induction agent.
The median age was 60 years (range, 26-88) in the obinutuzumab arm and 58 years (range, 23-85) in the rituximab arm. The majority of patients were women in both arms. In the experimental arm, 78.7% had intermediate- or high-risk disease by Follicular Lymphoma International Prognostic Index (FLIPI) score, as did 79.2% of the patients in the control arm.
An interim analysis performed at a median follow-up of 34.5 months (range, 0-54.5), showed a 3-year PFS rate of 80.0% with obinutuzumab compared with 73.3% with rituximab (HR, 0.66; 95% CI, 0.51-0.85; P = .001). Response rates were also similar between the 2 groups, at 88.5% and 86.9%, respectively.2
At a median follow-up of 57.3 months, obinutuzumab-based therapy was associated with a 4-year PFS rate of 78.1% compared with 67.2% with rituximab-based therapy (HR, 0.73; 95% CI, 0.59-0.90; P = .0034). The 4-year overall survival (OS) rates were similar, at 92.6% and 90.3%, respectively.3
In this final analysis, Townsend said obinutuzumab improved 7-year PFS across most subgroups, although results in those with low-risk disease slightly favored rituximab (65.4% vs 70.9%; HR, 1.20; 95% CI, 0.75-1.90; P = 0.45).In patients with intermediate- or high-risk FL, the 7-year PFS rate was 62.9% vs 51.8% (HR, 0.70; 95% CI, 0.57-0.86; P < .001) favoring obinutuzumab.
Townsend noted that obinutuzumab improved time to next lymphoma treatment (NLT). There were 160 (26.6%) NLT events in the experimental arm compared with 209 (34.8%) in the control arm. Furthermore, patients assigned to obinutuzumab were more likely to be free from NLT at 7 years (74.1% vs 65.4%; HR, 0.71; 95% CI, 0.58-0.87; P = .001).
“One potential criticism of PFS as the primary end point in first-line follicular [lymphoma] studies is that these patients underwent numerous scans at various time points after completing therapy and perhaps you pick up a number of progressions, radiologically, that aren’t clinically significant in follicular lymphoma,” Townsend said. “So, it is reassuring to see that the perhaps more subjective but clinically meaningful end point of time to next treatment is similarly improved with obinutuzumab, with a similar order of magnitude as the PFS benefit.”
The 7-year OS rates were similar with obinutuzumab and rituximab, at 88.5% and 87.2%, respectively (HR, 0.86; 95% CI, 0.63-1.18; P = .36).
PET response status at end of induction (EOI) was associated with improved survival. Investigators performed a retrospective analysis of 519 patients who underwent PET at EOI. Patients who had compete metabolic response (CMR) had superior 7-year PFS (57.2% vs 26.5%; HR, 0.31; 95% CI, 0.22-0.46; P < .0001) compared with those who did not. The result was similar for OS (90.2% vs 73.2%; HR, 0.30; 95% CI, 0.18-0.52; P < .0001).
Townsend noted that those who had CMR with obinutuzumab had superior PFS results for those who did so with rituximab. The 7-year PFS rate for those who had CMR on obinutuzumab was 62.5% compared with 51.4% for rituximab (HR, 0.72; 95% CI, 0.52-0.99; P = .04). OS results following CMR were similar irrespective of treatment (90.6% vs 89.8%; HR, 1.09; 95% CI, 0.61-1.93; P = 0.77).
“Those who did not achieve metabolic remission is a relatively small group and confidence intervals therefore are wide,” Townsend said. “But again, it appears that those patients not achieving metabolic remission in [the] obinutuzumab arm may derive more benefit than the induction [with rituximab].”
The rates of grade 3 or higher adverse effects (AEs) and serious AEs were 79.2% and 48.7% in the obinutuzumab arm vs 71.2% and 42.2% with rituximab-based therapy at the 4-year follow-up. Townsend said investigators did not observe any new safety signals in this analysis.
In the observation/follow-up phase, 21.3% of patients in the experimental arm had experienced grade 3 or higher AEs and 17.2% have experienced serious AEs. Those results are 15.7% and 14.5%, respectively, in the rituximab arm.
There were no grade 3 or higher infusion-related reactions in this phase. In the experimental arm, investigators observed grade 3 or higher neutropenia in 3.5% of patients and grade 3 or higher infections in 8.7%. In the control arm, 1.7% of patients experienced grade 3 or higher neutropenia and 5.8% experienced grade 3 or higher infections.