@article{6769937a1d7d43638b789083169c7412,
title = "The impact of dose modification and temporary interruption of ibrutinib on outcomes of chronic lymphocytic leukemia patients in routine clinical practice",
abstract = "To study the impact of dose modification and temporary interruption of ibrutinib in routine clinical practice, we conducted a retrospective study of consecutive CLL patients treated with ibrutinib outside the context of a clinical trial at Mayo Clinic, (Rochester, MN) from 11/2013 to 12/2017. Of 209 patients, 131 (74%) had unmutated IGHV, 38 (20%) had TP53 disruption, and 47 (22%) were previously untreated. A total of 87/209 (42%) patients started reduced dose ibrutinib (<420 mg daily; n = 43, physician preference; n = 33, concomitant medications; and n = 11, other). During 281 person-years of treatment, 91/209 patients had temporary dose interruption (54%, nonhematologic toxicity; 29%, surgical procedures; 10%, hematologic toxicity; and 7%, other). After a median follow-up of 24 months, the estimated median event-free survival (EFS) was 36 months, and median overall survival (OS) was not reached. On multivariable analyses, temporary ibrutinib interruption (hazard ratio [HR]: 2.37, P =.006) and TP53 disruption at ibrutinib initiation (HR: 1.81, P =.048) were associated with shorter EFS, whereas only TP53 disruption (HR: 2.38, P =.015) was associated with shorter OS. Initial ibrutinib dose and dose modification during therapy did not appear to impact EFS or OS. These findings illustrate the challenges associated with continuous oral therapy with ibrutinib in patients with CLL.",
author = "Parikh, {Sameer A.} and Achenbach, {Sara J.} and Call, {Timothy G.} and Rabe, {Kari G.} and Wei Ding and Leis, {Jose F.} and Kenderian, {Saad S.} and Chanan-Khan, {Asher A.} and Koehler, {Amber B.} and Schwager, {Susan M.} and Eli Muchtar and Fonder, {Amie L.} and McCullough, {Kristen B.} and Nedved, {Adrienne N.} and Smith, {Matthew D.} and Slager, {Susan L.} and Kay, {Neil E.} and Finnes, {Heidi D.} and Shanafelt, {Tait D.}",
note = "Funding Information: This work was supported by Pharmacyclics. Sameer A. Parikh and Saad S. Kenderian are Scholars in the Mayo Clinic Paul Calabresi Program in Translational Research (K12 CA090628). Drs. Shanafelt and Kay were supported by CA197130. SAP, HDF, and TDS designed the research, collected, analyzed and interpreted data, cared for the patients and wrote the manuscript. TGC, WD, JFL, SSK, AAC, ABK, EM, ALF, KBM, ANN, and MDS cared for the patients, analyzed data, and critically reviewed the manuscript. SJA, KGR, SMS, and SLS collected and analyzed data, conducted statistical analysis, and critically reviewed the manuscript. All authors approved the manuscript in its final format. Funding Information: This work was supported by Pharmacyclics. Sameer A. Parikh and Saad S. Kenderian are Scholars in the Mayo Clinic Paul Calabresi Program in Translational Research (K12 CA090628). Drs. Shanafelt and Kay were supported by CA197130. SAP, HDF, and TDS designed the research, collected, analyzed and interpreted data, cared for the patients and wrote the manuscript. TGC, WD, JFL, SSK, AAC, ABK, EM, ALF, KBM, ANN, and MDS cared for the patients, analyzed data, and critically reviewed the manuscript. SJA, KGR, SMS, and SLS collected and analyzed data, conducted statistical analysis, and critically reviewed the manuscript. All authors approved the manuscript in its final format. Publisher Copyright: {\textcopyright} 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",
year = "2020",
month = may,
day = "1",
doi = "10.1002/cam4.2998",
language = "English (US)",
volume = "9",
pages = "3390--3399",
journal = "Cancer medicine",
issn = "2045-7634",
publisher = "John Wiley and Sons Ltd",
number = "10",
}