Patient-reported health-related quality of life in previously untreated chronic lymphocytic leukaemia: Results from the randomised phase 3 FLAIR trial comparing ibrutinib-rituximab versus fludarabine-cyclophosphamide-rituximab.

Front-Line therapy in CLL: Assessment of Ibrutinib-containing Regimens (FLAIR) demonstrated improved progression-free survival for ibrutinib and rituximab (IR) compared with fludarabine, cyclophosphamide and rituximab (FCR) in previously untreated chronic lymphocytic leukaemia (CLL). This report presents the secondary end-point of health-related quality of life (HR-QoL). FLAIR was a phase 3, open-label, randomised trial across 101 hospitals. Eligible patients were aged 18-75 years, World Health Organization performance status (PS) ≤2, requiring treatment; those with >20% 17p deletion were excluded. IR was administered for up to 6 years and FCR for six cycles. Participants completed European Organisation for Research and Treatment of Cancer Quality of Life C30 Questionnaire (EORTC-QLQ-C30), QLQ CLL Module (QLQ-CLL16), three-level EQ-5D (EQ-5D-3L) and EQ5D visual analogue (EQ-VAS) at baseline and follow-up. Function and symptom trajectories were analysed using repeated-measures multilevel regression. 84.4% of participants completed baseline questionnaires and subsequent compliance was 67.6%-83.5%. Median age was 63 years; most participants were white and male. HR-QoL trajectories were similar. FCR recipients had worse scores at end of treatment but recovered thereafter. By 48 months, more FCR-treated participants showed meaningful improvements in several scales. Statistically significant differences (p < 0.05) favoured IR for physical, role and social function; emotional function favoured FCR. Diarrhoea was more common with IR; fatigue and dyspnoea were more common with FCR, though differences did not exceed minimally important thresholds. Overall, scales were comparable between treatment groups, indicating that continuous IR does not compromise HR-QoL.