Carole Bitar1, Mohammed Z H Farooqui2, Janet Valdez2, Nakhle S Saba3, Susan Soto2, Amanda Bray2, Gerald Marti2, Adrian Wiestner2, Edward W Cowen4. 1. Department of Medicine, Tulane University, New Orleans, Louisiana2Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. 2. Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. 3. Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland3Section of Hematology and Medical Oncology, Department of Medicine, Tulane University, New Orleans, Louisiana. 4. Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
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.
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.
Authors: Tania Cristina de Sá Dias; André Rolim Baby; Telma Mary Kaneko; Maria Valéria Robles Velasco Journal: J Cosmet Dermatol Date: 2007-03 Impact factor: 2.696
Authors: Peter C M van de Kerkhof; Marcel C Pasch; Richard K Scher; Martina Kerscher; Uwe Gieler; Eckard Haneke; Philip Fleckman Journal: J Am Acad Dermatol Date: 2005-10 Impact factor: 11.527
Authors: Ranjana H Advani; Joseph J Buggy; Jeff P Sharman; Sonali M Smith; Thomas E Boyd; Barbara Grant; Kathryn S Kolibaba; Richard R Furman; Sara Rodriguez; Betty Y Chang; Juthamas Sukbuntherng; Raquel Izumi; Ahmed Hamdy; Eric Hedrick; Nathan H Fowler Journal: J Clin Oncol Date: 2012-10-08 Impact factor: 44.544
Authors: Michael L Wang; Simon Rule; Peter Martin; Andre Goy; Rebecca Auer; Brad S Kahl; Wojciech Jurczak; Ranjana H Advani; Jorge E Romaguera; Michael E Williams; Jacqueline C Barrientos; Ewa Chmielowska; John Radford; Stephan Stilgenbauer; Martin Dreyling; Wieslaw Wiktor Jedrzejczak; Peter Johnson; Stephen E Spurgeon; Lei Li; Liang Zhang; Kate Newberry; Zhishuo Ou; Nancy Cheng; Bingliang Fang; Jesse McGreivy; Fong Clow; Joseph J Buggy; Betty Y Chang; Darrin M Beaupre; Lori A Kunkel; Kristie A Blum Journal: N Engl J Med Date: 2013-06-19 Impact factor: 91.245
Authors: John C Byrd; Richard R Furman; Steven E Coutre; Ian W Flinn; Jan A Burger; Kristie A Blum; Barbara Grant; Jeff P Sharman; Morton Coleman; William G Wierda; Jeffrey A Jones; Weiqiang Zhao; Nyla A Heerema; Amy J Johnson; Juthamas Sukbuntherng; Betty Y Chang; Fong Clow; Eric Hedrick; Joseph J Buggy; Danelle F James; Susan O'Brien Journal: N Engl J Med Date: 2013-06-19 Impact factor: 91.245