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

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 ³6 point worsening from Baseline (ITT population)

Table 1. Summary of Definitive Improvement in FACT-Lym (ITT population)