ASH 2016 Abstract 6. 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
Robert E Marcus et al.
Results: Results are reported for 1202 FL pts (R-chemo, 601; G-chemo, 601) with a median age of 59 yrs (53.2% female); data for 195 MZL pts will be reported elsewhere. Treatment arms were well balanced by disease stage (Ann Arbor: I, 1.5%; II, 7.1%; III, 34.9%; IV, 56.5%) and prognostic factors (FLIPI: 0+1, 21.0%; 2, 37.2%; ≥3, 41.8%; FLIPI-2: 0, 9.1%; 1+2, 50.3%; ≥3, 40.6%). Chemotherapy received was B in 57.1% of pts, CHOP in 33.1%, and CVP in 9.8%. CR and ORR at EOI based on CT/NMR imaging were similar for the two arms. After a median follow-up of 34.5 mo (range, 0–54.5), there was a 34% reduction in the risk of progression or death (HR, 0.66; 95% CI, 0.51, 0.85; p=0.001). Although medians have not been reached in GALLIUM or PRIMA, the observed HR of 0.66 would translate to a 1.5x longer median PFS for G-chemo than R-chemo, and to an estimated 3 yr improvement in the G arm if a median PFS of 6 yrs was assumed in the R arm. Three-yr INV-assessed PFS rates were: G-chemo, 80.0% (95% CI, 75.9%, 83.6%); R-chemo, 73.3% (95% CI, 68.8%, 77.2%). A consistent benefit in favor of G-chemo was also seen for PFS assessed by Independent Review Committee (IRC), as well as other time-to-event endpoints (Table 1). Subgroup analyses were broadly consistent with the primary analysis. At the time of the analysis, 35 pts (G-chemo; 5.5%) and 46 pts (R-chemo; 8.7%) had died (HR for overall survival, 0.75; 95% CI, 0.49, 1.17; p=0.210; Table 1). G-chemo pts had a higher frequency of grade 3–5 AEs (74.6%) and SAEs (46.1%) than R-chemo pts (67.8% and 39.9%, respectively). The frequency of fatal AEs was similar (G-chemo, 4.0%; R-chemo, 3.4%). AEs led to treatment discontinuation in 16.3% pts (G-chemo) and 14.2% pts (R-chemo) in the absence of disease progression. The median decrease in IgG levels at the EOI treatment was similar in the two arms.
Conclusion: In pts with previously-untreated FL, G-based immunochemotherapy and maintenance resulted in a clinically meaningful improvement in PFS, with a 34% reduction in the risk of a PFS event relative to R-based therapy. Frequency of some AEs, e.g. infusion-related reactions (IRRs), cytopenias, and infections, was higher with G. These data support G-chemo becoming a new SoC in previously untreated pts with FL.
ASH 2016 Abstract 615. Obinutuzumab plus Bendamustine Followed by Obinutuzumab Maintenance Prolongs Overall Survival Compared with Bendamustine Alone in Patients with Rituximab-Refractory Indolent Non-Hodgkin Lymphoma: Updated Results of the GADOLIN Study
Bruce D. Cheson et al.
Results: Figure 1. OS results: A) ITT population; B) FL pts
Conclusions: Updated analysis of the GADOLIN study with ~10 mo additional follow-up confirms the previously reported PFS benefit of G-B over B in pts with rituximab-refractory iNHL, and demonstrates a significant improvement in OS in the G-B arm. No new safety signals were detected.
CARE™ Faculty Perspective: The phase III RCTs, GALLIUM and GADOLIN, investigated the use of obinutuzumab in the front-line and relapsed/refractory FL settings respectively. Both studies were positive and reported significant improvements in PFS in the obinutuzumab arms. Additionally, results from the GADOLIN trial demonstrated an OS benefit for the Obinutuzumab and bendamustine combination. It is anticipated that these trials will be practice changing in the Canadian landscape, and that Obinutuzumab may soon replace rituximab as the immunotherapy standard of care in FL.
Additional abstract of interest: 613. Minimal Residual Disease in Patients with Follicular Lymphoma Treated with Obinutuzumab or Rituximab As First-Line Induction Immunochemotherapy and Maintenance in the Phase 3 GALLIUM Study