Primary Results of the Health-Related Quality of Life Assessment from the Phase III Gadolin Study of Obinutuzumab Plus Bendamustine Compared with Bendamustine Alone in Patients with Rituximab-Refractory, Indolent Non-Hodgkin Lymphoma

Abstract Background Meaningful improvement in, or maintenance of, pre-treatment health-related quality of life (HRQoL) is important for rituximab-refractory (R-ref), indolent non-Hodgkin lymphoma patients. GADOLIN (NCT01059630) is an open-label, phase III study of bendamustine (B) with or without obinutuzumab (GA101; Gazyva/Gazyvaro; G) in patients with CD20+ R-ref, indolent non-Hodgkin lymphoma. In GADOLIN, independent review facility (IRF)-assessed median progression-free survival (PFS) was 14.9 months (mo) in the B arm and not reached in the G-B arm (HR=0.55; 95% CI, 0.40, 0.74; p=0.0001), with an acceptable safety profile. Here, we present patient-reported HRQoL data from GADOLIN. Methods The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) questionnaire (Webster K, et al. Qual Life Res 2005;14:2103) was used to assess overall HRQoL, physical and functional well-being, and disease- and treatment-related symptoms. It was administered on day 1 of cycles 1, 3 and 5 during treatment, at the end of induction (EOI) treatment and every other month for 2-years (where non-progressing G-B patients received G maintenance and B patients were observed), and during follow-up. Time to ³6 point worsening from baseline in the FACT-Lym Trial Outcome Index (TOI) was estimated for each treatment group using a Kaplan-Meier curve. Minimally important differences at the individual subscale and total score levels were used to define the proportion of patients reporting improvement on the FACT-Lym lymphoma subscale (³3 points), TOI (³6 points), and lymphoma total score (³7 points). Results The primary study analysis was undertaken when 396 patients had been randomized (194 to G-B and 202 to B [198 treated]); median observation time was 21 mo. Baseline characteristics were balanced between arms. Median age was 63 years and patients had a median of two prior therapies. Questionnaire completion rates were generally good and balanced in the G-B vs B arms (91.2% vs 89.1% at baseline, 74.2% vs 69.8% at EOI, and 33.0% vs 31.2% at final follow up, respectively). Time to ³6 point worsening from baseline on the FACT-Lym TOI was 8.0 mo (95% CI, 5.8, 15.1) in the G-B arm and 4.6 mo (95% CI, 3.8, 6.4) in the B arm (HR, 0.74; 95% CI, 0.56, 0.98; Figure 1). In addition, a greater proportion of patients reported meaningful improvement on the lymphoma subscale, lymphoma TOI, and total score in the G-B arm than in the B arm throughout the study (Table 1). Conclusions G combined with B, followed by G maintenance, resulted in a greater proportion of patients reporting a meaningful improvement in HRQoL throughout the course of the study. This improvement occurred even during induction, despite similar clinical response rates. A longer time to clinically meaningful deterioration of lymphoma-related HRQoL compared with patients who received B alone was also observed. These results are consistent with the improvement in PFS and suggest that the improvement in PFS is not at the expense of an increase in treatment-related toxicity that could lead to a reduction in a patient's HRQoL. Figure 1. Kaplan-Meier Plot of FACT-Lym Trial Outcome Index ³ 6 point worsening from Baseline (ITT population) Figure 1. Kaplan-Meier Plot of FACT-Lym Trial Outcome Index ³ 6 point worsening from Baseline (ITT population) Figure 2. Summary of Definitive Improvement in FACT-Lym (ITT population) Figure 2. Summary of Definitive Improvement in FACT-Lym (ITT population) Disclosures Cheson: Celgene: Consultancy, Research Funding; AstraZeneca: Consultancy; Gilead: Consultancy, Research Funding; Spectrum: Consultancy; MedImmune: Research Funding; Teva: Research Funding; Pharmacyclics: Consultancy, Research Funding; Ascenta: Research Funding; Roche/Genentech: Consultancy, Research Funding; Astellas: Consultancy. Off Label Use: Obinutuzumab (GA101; Gazyva/Gazyvaro) is a CD20-directed cytolytic antibody and is indicated, in combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia). This abstract reports on bendamustine with or without obinutuzumab in patients with CD20+ R-ref, indolent non-Hodgkin lymphoma.. Trask:Genentech: Employment. Gribben:Janssen: Honoraria; Pharmacyclics: Honoraria; Celgene: Consultancy, Honoraria; Gilead: Honoraria; Roche/Genentech: Honoraria. Dimier:Roche: Employment. Kimby:Pfizer: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lugtenburg:Mundipharma: Consultancy; Servier: Consultancy; Janssen-Cilag: Consultancy; Celgene: Consultancy; Roche: Consultancy. Thieblemont:St. Louis Hospital, Paris, France: Employment. Wassner Fritsch:Roche: Employment. Sehn:Roche/Genentech: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria.

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