CLL patients treated with ibrutinib: incidence of brittle nails and hair changes

Ibrutinib is administered until disease progression or intolerable and/or severe toxic effects occur. However, cutaneous toxicity represents a potential barrier to long-term tolerability. The aim of the article was to establish hair and nail manifestations associated with the long-term use of ibrutinib for the treatment of CLL. This article was published by Bitar C et al., from the Tulane School of Medicine, New Orleans; in the journal of JAMA Dermatology in Jun 2016.

The main objectives of the paper were:

• Analysing nail and hair changes associated with ibrutinib therapy assessed by an 11-question survey.
• Determining the severity of nail changes from a 0 to 3 rating scale for both onychoschizia and onychorrhexis.

The key findings were as follows:

• Out of 66 patients (43 men and 23 women with ages ranging from 55 to 85 years), 44 (67%) of the patients reported brittle fingernails at a median of 6.5 months after starting ibrutinib therapy
• Fifteen patients (23%) developed brittle toenails after a median of 9 months of ibrutinib therapy
• Hair textural changes were reported in 17 patients (26%), at a median of 9 months of ibrutinib treatment.

Conclusions

Concern over cosmetic appearance and nail discomfort may negatively affect quality of life in diseases affecting the nails. The article reports that hair and nail abnormalities are commonly associated with ibrutinib and are known to appear several months after initiating therapy. Treatment options for brittle nails include biotin supplementation and topical solutions such as hydrosoluble nail lacquer and poly-ureaurethane. Ibrutinib covalently binds to the cysteine residue at the active site of BTK; because cysteines are critical for nail hardness, ibrutinib-induced disruption of the disulfide bonds between cysteine residues could be responsible for increased nail brittleness; however, this mechanism remains to be investigated.

The trial can be found at ClinicalTrials.gov (NCT01500733). The complete article can be found here.

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 ibrutinibtreatment.

CONCLUSIONS AND RELEVANCE:

Hair and nail abnormalities are commonly associated with ibrutinib and appear several months after initiatingtherapy. 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.