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FLAIR

Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis

Phase 3N = 771

Population
Previously untreated CLL requiring treatment, age 18-75 years, WHO performance status 2 or less, without more than 20% 17p-deleted CLL cells
Design
Open-label randomised phase 3 trial at 101 UK National Health Service hospitals; patients aged 18-75 with WHO performance status 2 or less and disease requiring treatment, excluding more than 20% of CLL cells with 17p deletion, randomly assigned 1:1 to ibrutinib-rituximab (ibrutinib up to 6 years) or FCR. Primary endpoint PFS, analysed by intention to treat. Registered as ISRCTN01844152 and EudraCT 2013-001944-76 (no ClinicalTrials.gov number in the abstract).
Primary endpoint
PFS
Arms
  • Ibrutinib-rituximab (experimental, n = 386): Ibrutinib 420 mg/day orally for up to 6 years plus rituximab for six 28-day cycles
  • FCR (control, n = 385): Fludarabine, cyclophosphamide and rituximab for up to six cycles
People
Hillmen P, senior author Munir T
PFSHR 0.44 (95% CI 0.32–0.60)
Show the numbers
Results reported for FLAIR
EndpointAnalysisIbrutinib-rituximabFCREffect
PFSinterimmedian follow-up 53 monthsHillmen 2023—median 67 monthsHR 0.44 (95% CI 0.32–0.60)P<0.0001Prespecified interim analysis. Median PFS not reached with ibrutinib-rituximab; 95% CI for the FCR median 63 months to not reached. Median follow-up IQR 41-61 months. The authors state that overall survival was not improved.
Results reported for FLAIR
EndpointAnalysisIbrutinib-rituximabFCREffect
PFSinterimmedian follow-up 53 monthsHillmen 2023—median 67 monthsHR 0.44 (95% CI 0.32–0.60)P<0.0001Prespecified interim analysis. Median PFS not reached with ibrutinib-rituximab; 95% CI for the FCR median 63 months to not reached. Median follow-up IQR 41-61 months. The authors state that overall survival was not improved.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.440.32–0.6
Illustrative — modelled from reported values, not trial data. PFS, interim.
0%25%50%75%100%050100150Months (modelled)
  • FCR (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsFCR
0100.0%
4264.8%
8441.9%
12627.2%
16817.6%
Primary publication: Hillmen P, Pitchford A, Bloor A, Broom A, Young M, Kennedy B, et al. Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(5):535-552. PubMedDOI

Appears in

Sources

  1. Hillmen P, Pitchford A, Bloor A, Broom A, Young M, Kennedy B, et al. Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(5):535-552.

    PubMedDOI