Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib

Blood. 2015 Mar 26;125(13):2062-7. doi: 10.1182/blood-2014-09-603670. Epub 2015 Jan 8.

Abstract

Ibrutinib is a Bruton tyrosine kinase 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 or without rituximab, at our center. Thirty-three (26%) patients have discontinued ibrutinib to date. The majority of those patients had high-risk features: 94% with unmutated immunoglobulin heavy chain variable gene rearrangement, 58% with del(17p) by fluorescence in situ hybridization, 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 miscellaneous reasons (2). Twenty five patients (76%) died after discontinuing ibrutinib; the median overall survival was 3.1 months after discontinuation. Most patients with RR-CLL who discontinued ibrutinib early were difficult to treat and had poor outcomes.

MeSH terms

  • Adenine / analogs & derivatives
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Cell Transformation, Neoplastic / chemically induced
  • Clinical Trials as Topic / mortality
  • Disease Progression
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis*
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Middle Aged
  • Piperidines
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Retrospective Studies
  • Survival Analysis
  • Withholding Treatment* / statistics & numerical data

Substances

  • Antineoplastic Agents
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Adenine