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.

Phase 3 FLAIR trial patients with previously untreated CLL (age 18–75, PS ≤2, no >20% del(17p)) were randomized to ibrutinib + rituximab given continuously for up to 6 years versus six cycles of fludarabine, cyclophosphamide, and rituximab. This analysis reports the secondary endpoint of health-related quality of life (HR‑QoL).

HR‑QoL was assessed using EORTC QLQ‑C30, QLQ‑CLL16, EQ‑5D‑3L, and EQ‑VAS at baseline and serially. Baseline completion was high (84.4%), with 67.6%–83.5% completion thereafter. Median age was 63 years; most were white and male.

Key findings on HR‑QoL:

• Overall trajectories: Overall HR‑QoL trajectories were broadly similar between arms.
• Chemoimmunotherapy impact: Patients on chemoimmunotherapy had worse HR‑QoL at the end of treatment but largely recovered thereafter.
• Longer-term improvement: By 48 months, a greater proportion of those treated with fludarabine-based therapy showed clinically meaningful improvements in several scales.

Functioning and symptoms:

• Functioning domains: Statistically significant differences favored ibrutinib‑rituximab for physical, role, and social functioning, while emotional functioning favored fludarabine-based therapy.
• Symptoms: Diarrhea was more frequent with ibrutinib‑rituximab; fatigue and dyspnea were more common with fludarabine-based therapy, though between‑group differences in symptoms generally did not exceed minimally important thresholds.

Overall, continuous ibrutinib‑rituximab did not compromise HR‑QoL compared with finite fludarabine, cyclophosphamide, and rituximab, despite prolonged treatment duration.