In the final analysis of the GADOLIN study in patients with rituximab-refractory indolent non-Hodgkin lymphoma, the combination of obinutuzumab plus bendamustine reduced the risk of progression or death by 43% compared with bendamustine alone. In patients with follicular lymphoma, the reduction was 49%.
Laurie H Sehn, MD
In the final analysis of the GADOLIN (NCT01059630) study in patients with rituximab (Rituxan)-refractory indolent non-Hodgkin lymphoma (iNHL), the combination of obinutuzumab (Gazyva) plus bendamustine reduced the risk of progression or death by 43% compared with bendamustine alone. In patients with follicular lymphoma (FL), the reduction was 49%. The combination therapy provided a sustained and clinically relevant overall survival (OS) benefit with no new safety signals with longer follow-up time.
The open-label, randomized, phase 3 study compared the efficacy and safety of obinutuzumab plus bendamustine induction, followed by obinutuzumab maintenance with bendamustine induction in rituximab-refractory iNHL. Laurie H Sehn, MD, BC Cancer Centre for Lymphoid Cancer and the University of British Columbia, Vancouver, Canada, presented a poster of the final data with safety follow-up data for all patients (2 years of safety data from the last dose; data cutoff November 30, 2018) at the 2019 American Society of Hematology Annual Meeting.1
Patients (N = 413) age ≥18 years with documented rituximab-refractory iNHL and an ECOG performance status of 02 were randomly assigned to either obinutuzumab 1000 mg intravenously (IV) days 1, 8, and 15 of cycle 1, and day 1 of cycles 2–6 plus bendamustine 90 mg/m2/day IV of days 1 and 2 of cycles16 (n = 204) or to bendamustine monotherapy (120 mg/m2/day IV days 1 and 2 of cycles16 in 28-day cycles (n = 209).
Following induction, patients in the combination arm without evidence of progression received obinutuzumab maintenance (1000 mg IV every 2 months for 2 years or until disease progression). Final analysis end points included investigator-assessed progression-free survival (PFS), OS, time to new anti-lymphoma treatment (TTNT), and safety. The safety population included patients who received ≥1 dose of study treatment, excluding 2 patients crossing over to the combination arm during maintenance.
Of 413 iNHL patients in the intent to treat (ITT) population (n = 335), 164 in the combination arm and 171 in the bendamustine arm had FL. Median (range) observation time was 57.5 (0.497.6) months for the combination arm and 47.9 (0–100.9) months for the bendamustine arm (ie, 27.6 and 35.6 months additional follow-up since the primary analysis).
Median investigator-assessed PFS was 25.8 months for the combination versus 14.1 months for bendamustine (HR, 0.57; 95% CI, 0.45-0.73;P<.0001) in all patients. For patients with FL, median PFS was 24.1 for the combination versus 13.7 months for bendamustine (HR, 0.51; 95% CI, 0.39-0.67;P<.0001).
For all patients, median OS was 88.3 months for the combination versus 65.6 months for bendamustine (HR, 0.77; 95% CI, 0.57-1.03;P= .0810; 23% risk reduction). For patients with FL, median OS was not reached in the combination arm versus 60.3 months for bendamustine (HR, 0.71; 95% CI, 0.51-0.98;P= .0343).
Median TTNT was longer with obinutuzumab plus bendamustine than for bendamustine alone: for all patients it was 38.2 versus 18.9 months, respectively (HR, 0.60; 95% CI, 0.47- 0.76), and for patients with FL it was 33.6 versus 18.0 months, respectively (HR, 0.56; 95% CI, 0.43- 0.73).
Overall, fewer patients died in the combination arm (84 out of 204; 41.2%) than in the bendamustine arm (100 out of 203; 49.3%).
The safety population (N = 407) included 204 patients in the combination arm and 203 patients in the bendamustine arm. Grade ≥3 adverse events (AEs) occurred in 73.0% of patients in the combination arm and 66.0% of patients in the bendamustine arm.
Grade ≥3 AEs that were more frequent in the obinutuzumab plus bendamustine arm than the bendamustine arm included neutropenia (37.3% vs 30.0%) and infusion-related reactions (11.3% vs 5.4%); those that were more frequent in the bendamustine arm than the combination arm included thrombocytopenia (15.8% vs 10.8%) and anemia (10.8% vs 7.4%). The incidences of grade ≥3 infections (22.5% vs 19.2%) and grade ≥3 second malignancies (7.8% vs 5.9%) were similar between the combination and monotherapy arms, respectively.
Serious AEs occurred in 44.6% of patients in the combination arm and 37.4% of patients in the bendamustine arm; fatal AEs occurred in 9.8% and 7.4% of patients, respectively. The most frequent AE leading to death in the obinutuzumab plus bendamustine versus bendamustine arms were infections (6 vs 7 patients, respectively) and second malignancies (8 vs 4 patients, respectively). Safety results for patients with FL were comparable with those for the overall iNHL population.
Reference:Sehn LH, Trněný M, Bouabdallah K, et al. Sustained overall survival benefit of obinutuzumab plus bendamustine followed by obinutuzumab maintenance compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma: final results of the Gadolin study. Presented at: American Society of Hematology Annual Meeting; December 7-10, 2019; Orlando, FL. Abstract 2822. https://bit.ly/38nMoqz.