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Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib

John C. Byrd, Richard R. Furman, Steven E. Coutre, Jan A. Burger, Kristie A. Blum, Morton Coleman, William G. Wierda, Jeffrey A. Jones, Weiqiang Zhao, Nyla A. Heerema, Amy J. Johnson, Yun Shaw, Elizabeth Bilotti, Cathy Zhou, Danelle F. James and Susan O'Brien

Key points

  • 3-year follow-up of ibrutinib in CLL demonstrated continued activity with durable responses that improve in quality with extended treatment.

  • Toxicity diminished over time with respect to grade ≥ 3 cytopenias, fatigue, infections, and adverse events leading to discontinuation.

Abstract

Ibrutinib is an orally administered inhibitor of Bruton's tyrosine kinase that antagonizes B-cell receptor, chemokine, and integrin-mediated signaling. In early-phase studies, ibrutinib demonstrated high response rates and prolonged progression-free survival (PFS) in CLL. The durable responses observed with ibrutinib relate in part to a modest toxicity profile that allows the majority of patients to receive continuous therapy for an extended period. We report on median 3-year follow-up of 132 patients with symptomatic treatment-naïve and relapsed/refractory CLL or SLL. Longer treatment with ibrutinib was associated with improvement in response quality over time and durable remissions. Toxicity with longer follow-up diminished with respect to occurrence of grade 3 or greater cytopenias, fatigue, and infections. Progression remains uncommon, occurring primarily in some patients with relapsed del(17)(p13.1) and/or del(11)(q22.3) disease. Treatment-related lymphocytosis remains largely asymptomatic even when persisting >1 year and does not appear to alter longer-term PFS and overall survival compared to patients with partial response or better. Collectively, these data provide evidence that ibrutinib controls CLL disease manifestations and is well tolerated for an extended period; this information can help direct potential treatment options for different subgroups to diminish the long-term risk of relapse.

  • Submitted October 31, 2014.
  • Accepted February 3, 2015.