Hair and Nail Changes During Long-term Therapy With Ibrutinib for Chronic Lymphocytic Leukemia

JAMA Dermatol. 2016 Jun 1;152(6):698-701. doi: 10.1001/jamadermatol.2016.0225.

Abstract

Importance: Ibrutinib, a Bruton tyrosine kinase inhibitor, is a new targeted agent approved by the US Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma, and Waldenström macroglobulinemia. Ibrutinib is overall well tolerated but long-term treatment is required until disease progression or intolerable toxic effects occur. Little is known regarding its cutaneous adverse effects.

Objective: To describe the hair and nail manifestations associated with the long-term use of ibrutinib for the treatment of CLL.

Design, setting, and participants: Prospective study of 66 patients with CLL enrolled in a single-arm phase 2 clinical trial of ibrutinib for CLL between March 2014 and October 2015 at the National Institutes of Health.

Main outcomes and measures: The primary outcome, nail and hair changes associated with ibrutinib therapy, was assessed by an 11-question survey. In addition, the severity of nail changes was determined from a 0 to 3 rating scale for both onychoschizia and onychorrhexis.

Results: Among 66 patients (43 men and 23 women with ages ranging from 55 to 85 years), 44 (67%) reported brittle fingernails at a median of 6.5 (95% CI, 6-12) months after starting ibrutinib therapy. Fifteen patients (23%) developed brittle toenails after a median of 9 (95% CI, 6-15) months of ibrutinib therapy. Textural hair changes were reported in 17 patients (26%), at a median of 9 (95% CI, 6-12) months of ibrutinib treatment.

Conclusions and relevance: Hair and nail abnormalities are commonly associated with ibrutinib and appear several months after initiating therapy. Ibrutinib inhibits Bruton tyrosine kinase by covalently binding to cysteine 481. Whether ibrutinib affects the hair and nails by binding and altering cysteine-rich proteins of hair and nails or by means of another mechanism remains unknown.

Trial registration: clinicaltrials.gov Identifier: NCT01500733.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Female
  • Hair Diseases / chemically induced*
  • Hair Diseases / pathology
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Nail Diseases / chemically induced*
  • Nail Diseases / pathology
  • Piperidines
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects*
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects*
  • Severity of Illness Index
  • Time Factors

Substances

  • Antineoplastic Agents
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • Adenine

Associated data

  • ClinicalTrials.gov/NCT01500733