Health-Related Quality of Life in Patients with Advanced-Stage Follicular Lymphoma Receiving Consolidation with 90Y-Ibritumomab Tiuxetan (Zevalin®) of First Remission: Results from the Randomized Phase 3 First-Line Indolent Trial (FIT).
Authors: Gondek Kathleen , Shah Sonalee , Bischof-Delaloye Angelika , Rohatiner Ama , Salles Gilles , Putz Barbara , Kunz Michael , Hagenbeek Anton 
Published: October 2019

Abstract
A previous phase 3 study showed that in patients with relapsed/refractory low-grade, follicular or transformed non-Hodgkin’s lymphoma, radioimmunotherapy with 90Y-ibritumomab tiuxetan (Zevalin) significantly improved patient-reported quality of life (QoL) as measured by the validated Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire (Wiseman et al Blood2000;96(11):734a, abstract 3173). The study showed significant improvements in FACT-G total score, as well as in subscores for emotional, physical, and functional well-being. In the recent international phase 3 First-line Indolent Trial (FIT), patients with stage III or IV follicular lymphoma in first remission after initial chemotherapy were randomized to receive consolidation with Zevalin (n=208) or no further treatment (control; n=206). The impact of Zevalin on health-related QoL was evaluated as one of the secondary end points of this study. Health-related QoL was assessed using EORTC QLQ-C30 (version 2) and EuroQoL-5D (EQ-5D) questionnaires. The EORTC QLQ-C30 was developed to specifically assess QoL in patients with cancer, and comprises 30 items grouped into the following dimensions: functional (physical, role, cognitive, social, emotional), symptomatic (nausea, pain, fatigue), global QoL, and other (dyspnea, difficulty sleeping, anorexia, constipation, diarrhea, perceived financial difficulties). The EQ-5D was developed as a generic instrument to assess health-related QoL and comprises 2 sections, an assessment based on 5 dimensions (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression) and a visual analogue scale (VAS). These questionnaires were administered at the screening visit, week 14, every 6 months thereafter, and at the end of the follow-up period. Descriptive statistics were used to compare scores across treatment groups. The change in scores from baseline was also assessed by gender, age, and first-line treatment. Mixed effects model was used to assess factors associated with final scores of the VAS of EQ-5D. No notable treatment differences were observed in EORTC QLQ-C30 (all domains) scores across timepoints or changes from baseline. This result was true for all subgroups. The mean scores for EQ-5D at the screening and final visits were 0.83 and 0.84, respectively, for the Zevalin arm, and 0.84 and 0.83, respectively, for the control arm. The mean VAS scores at the screening and final visits were 77.52 and 77.64, respectively, for the Zevalin arm, and 76.57 and 78.60, respectively, for the control arm. An analysis of factors associated with final VAS scores showed that only baseline VAS scores affected final VAS scores (P<0.0001) considerably. No differences were observed in health-related QoL parameters between patients receiving consolidation therapy with Zevalin and patients in the control arm as measured by EORTC QLQ C-30 and EQ-5D questionnaires. Thus, in patients with advanced-stage follicular lymphoma responsive to first-line therapy, treatment with Zevalin consolidation does not impact the health-related QoL compared with no further treatment.