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Outcomes of patients with chronic lymphocytic leukemia (CLL) after discontinuing ibrutinib

Preetesh Jain, Michael Keating, William Wierda, Zeev Estrov, Alessandra Ferrajoli, Nitin Jain, Binsah George, Danelle James, Hagop Kantarjian, Jan Burger and Susan O'Brien

Key points

  • Clinical characteristics, causes of discontinuation and outcome of patients who progress or fail ibrutinib are described.

  • Patients with CLL who progress early on ibrutinib therapy have poor outcomes.

Abstract

Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment of patients with relapsed refractory chronic lymphocytic leukemia (RR-CLL). We describe the characteristics, causes of discontinuation and outcomes in patients who discontinued treatment with ibrutinib. One hundred twenty seven patients were enrolled in various clinical trials of ibrutinib with/without rituximab at our center. Thirty three (26%) patients have discontinued ibrutinib to date. The majority of those patients had high risk features; 94% unmutated IGHV, 58% with del(17p) by FISH, and 54% with a complex karyotype. Causes of discontinuation were disease transformation (7), progressive CLL (7), stem cell transplantation (3), adverse events (11), serious adverse events/deaths (3) and 2 had miscellaneous reasons. Twenty five patients (76%) died after discontinuing ibrutinib; the median overall survival was 3.1 months after discontinuation. Most relapsed refractory patients with CLL who discontinued ibrutinib early were difficult to treat and had poor outcomes.

  • Submitted September 29, 2014.
  • Accepted December 29, 2014.