Advertisement

Obinutuzumab-Based Immunochemotherapy Prolongs Progression-Free Survival and Time to Next Anti-Lymphoma Treatment in Patients with Previously Untreated Follicular Lymphoma: Four-Year Results from the Phase III GALLIUM Study

William Townsend, Christian Buske, Guillaume Cartron, David Cunningham, Martin JS Dyer, John G. Gribben, Georg Hess, Takayuki Ishikawa, Ulrich Keller, Michael Kneba, Ram Malladi, Jeffrey D Neidhart, Chiara Rusconi, Jun Zhu, Olivier Catalani, Andrea Knapp, Harald Zeuner, Michael Herold, Wolfgang Hiddemann and Robert Marcus

Abstract

Introduction: Immunochemotherapy is standard of care treatment for previously untreated patients (pts) with advanced stage follicular lymphoma (FL). However, the majority of pts relapse, with around 20% relapsing within 2 years. Obinutuzumab (GA101; G) is a glycoengineered type II anti-CD20 monoclonal antibody (mAb) with increased antibody-dependent cell-mediated phagocytosis and cytotoxicity, and direct B-cell killing, compared with the type I mAb rituximab (R). The randomized Phase III GALLIUM study (NCT01332968) compared the efficacy and safety of G-chemotherapy (G-chemo) vs R-chemotherapy (R-chemo) in previously untreated pts with advanced stage FL. In the primary analysis (PA), a significant improvement in the primary study endpoint of investigator (INV)-assessed progression-free survival (PFS) was demonstrated with G-chemo relative to R-chemo after 34.5 months' median follow-up. Results for other time-to-event outcomes (including time-to-next treatment; TTNT) were supportive, and additional analyses demonstrated a higher rate of minimal residual disease, and a lower risk of disease progression within 24 months, in the G-chemo arm. Here we report the results from an updated analysis of time-to-event endpoints and safety in the GALLIUM study.

Methods: In GALLIUM, enrolled pts were aged ≥18 years with previously untreated FL (grades 1-3a), Stage III/IV disease (or Stage II with bulky disease), and ECOG PS 0-2, and requiring treatment according to GELF criteria. Pts were randomized 1:1 to receive G 1000mg IV (days 1, 8 and 15 of cycle 1 and day 1 of subsequent cycles) or R 375mg/m2 IV (day 1 of each cycle) plus chemotherapy for 6 or 8 cycles, depending on the chemotherapy backbone (CHOP, CVP, or bendamustine). Chemotherapy backbone was a stratification factor and was chosen upfront by the participating centers. Pts with a complete or partial response at the end of induction received maintenance with the same antibody every 2 months for 2 years. The data cut-off for the current analysis was February 12, 2018.

Results: In total, 1202 pts with FL were enrolled (G-chemo, n=601; R-chemo, n=601), with a median age of 59 years (46.8% male). After 57.3 months' median follow-up, a sustained and clinically meaningful improvement in INV-assessed PFS was observed with G-chemo relative to R-chemo (HR 0.73; 95% CI: 0.59, 0.90; p=0.0034; 4-year PFS rate: G-chemo, 78.1% [95% CI: 74.4%, 81.3%]; R-chemo, 67.2% [95% CI: 63.1%, 71.0%]; Figure 1A). Since the PA, 114 new PFS events (57 in G-chemo and 57 in R-chemo) had occurred. Overall survival (OS) data, which remain immature, were comparable across treatment arms (HR 0.88; 95% CI: 0.61, 1.27; p=0.49; 4-year OS rate: G-chemo, 92.6% [95% CI: 90.1%, 94.4%]; R-chemo, 90.3% [95% CI: 87.6%, 92.5%]; Figure 1B). A sustained benefit in favor of G-chemo was observed in TTNT (HR 0.70; 95% CI: 0.54, 0.90; p=0.0046; 4-year TTNT rate: G-chemo, 84.2% [95% CI: 80.9%, 86.9%]; R-chemo, 76.7% [95% CI: 73.1%, 80.0%]; Figure 1C). Since the PA, 29 and 36 additional pts in the G- and R-chemo arms, respectively, had received new anti-lymphoma treatment. At cut-off, 54 (9.1%) pts in the G-chemo arm and 61 (10.2%) in the R-chemo arm had died. Common causes were disease progression (G-chemo, n=21 [3.5%]; R-chemo, n=28 [4.7%]) and AEs (G-chemo, n=24 [4.0%]; R-chemo, n=24 [4.0%]). The most common fatal AEs were infections (9 vs 4 pts, respectively) and new malignancies (5 vs 6 pts, respectively). Incidences of AEs of any grade were comparable across the G-chemo (99.8%) and R-chemo (99.5%) arms, although grade 3-5 AEs (79.2% vs 71.2%) and serious AEs (48.7% vs 42.2%) were more common in the G-chemo arm. AEs led to discontinuation in 16.3% of G-chemo pts and 14.6% of R-chemo pts. As in the PA, the incidence of grade 3-5 infections (22.2% vs 18.6%), grade 3-5 neutropenia (and associated complications reported as AEs, 48.4% vs 41.4 %), and grade 3-5 second malignancies (6.9% vs 4.4%) was numerically higher in pts receiving G-chemo than R-chemo.

Conclusions: In line with the PA, the results from this updated analysis of the GALLIUM study, with a median follow-up of almost 5 years, reinforce that G-chemo provides clinically meaningful improvements in outcomes relative to R-chemo in previously untreated FL pts. OS data remain immature, with additional follow-up needed to draw conclusions. Safety data are consistent with those reported in the PA.

Disclosures Townsend: Gilead: Consultancy; Roche: Consultancy. Buske: Roche: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Bayer: Research Funding. Cartron: Roche: Consultancy, Honoraria; Sanofi: Honoraria; Gilead Sciences: Honoraria; Janssen: Honoraria; Celgene: Consultancy, Honoraria. Cunningham: Roche pharmaceuticals: Research Funding. Dyer: Roche: Honoraria, Research Funding. Gribben: Medical Research Council: Research Funding; Acerta Pharma: Honoraria, Research Funding; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria, Research Funding; TG Therapeutics: Honoraria; Abbvie: Honoraria; Wellcome Trust: Research Funding; Unum: Equity Ownership; Pharmacyclics: Honoraria; NIH: Research Funding; Cancer Research UK: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Kite: Honoraria. Hess: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Other: travel expenses, Research Funding; CTI: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Keller: BMS: Consultancy; Celgene: Research Funding; MSD: Consultancy; Takeda: Consultancy, Research Funding; Janssen-Cilag: Consultancy, Equity Ownership; Roche: Consultancy. Kneba: Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Malladi: Roche: Membership on an entity's Board of Directors or advisory committees. Neidhart: Gilead: Consultancy; Roche: Consultancy, Other: Travel support and lecture fees. Rusconi: Celgene: Research Funding. Zhu: Beijing Cancer Hospital (Peking University Cancer Hospital): Employment. Catalani: Roche: Employment. Knapp: Roche: Employment. Zeuner: F. Hoffman-La Roche: Employment, Equity Ownership. Hiddemann: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Marcus: Roche: Consultancy, Other: Travel support and lecture fees ; Gilead: Consultancy; F. Hoffman-La Roche: Other: Travel support and lecture fees.

  • * Asterisk with author names denotes non-ASH members.