Open AccessThe impact of dose modification and temporary interruption of ibrutinib on outcomes of chronic lymphocytic leukemia patients in routine clinical practice
Author(s) -
Parikh Sameer A.,
Achenbach Sara J.,
Call Timothy G.,
Rabe Kari G.,
Ding Wei,
Leis Jose F.,
Kenderian Saad S.,
ChananKhan Asher A.,
Koehler Amber B.,
Schwager Susan M.,
Muchtar Eli,
Fonder Amie L.,
McCullough Kristen B.,
Nedved Adrienne N.,
Smith Matthew D.,
Slager Susan L.,
Kay Neil E.,
Finnes Heidi D.,
Shanafelt Tait D.
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2998
Subject(s) - ibrutinib , medicine , hazard ratio , concomitant , context (archaeology) , toxicity , ighv@ , retrospective cohort study , chronic lymphocytic leukemia , discontinuation , oncology , leukemia , confidence interval , paleontology , biology
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.