CLL: 17-gene signature predicts durable remission with frontline FCR

  • Herling CD & al.
  • Lancet Oncol
  • 30 Sep 2019

  • curated by David Reilly
  • Univadis Clinical Summaries
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Takeaway

  • A reproducible 17-gene signature successfully identified treatment-naive patients with immunoglobulin heavy chain gene (IGHV)-unmutated chronic lymphocytic leukemia (CLL) likely to achieve long-term remission after first-line fludarabine, cyclophosphamide, and rituximab (FCR).

Why this matters

  • Predicting response to FCR may better inform treatment selection.  

Study design

  • Study to develop a gene signature identifying patients with CLL likely to achieve durable remissions after FCR.
  • Transcriptional profiling was undertaken in 101 patients with CLL who received ≥3 cycles of FCR at the University of Texas MD Anderson Cancer Center (MDACC).
  • Findings were validated in 109 patients with FCR-treated IGHV-unmutated CLL from the CLL8 trial of the German Chronic Lymphocytic Leukaemia Study Group.
  • Funding: Chronic Lymphocytic Leukaemia Global Research Foundation and the National Institutes of Health/National Cancer Institute.

Key results

  • Analyses identified 17 genes differentiating patients with IGHV-unmutated status with intermediate or unfavorable risk for progression after first-line FCR: cause-specific HR, 3.83 (95% CI, 1.94-7.59; P<.0001>
  • On validation of the 17-gene signature in the CLL8 cohort:
    • Median time to progression in those with unfavorable prognosis, 39 (interquartile range [IQR], 22-69) months vs 59 (IQR, 28-84) months in those with intermediate prognosis.

Limitations

  • Retrospective data.