The impact of dose modification and temporary interruption of ibrutinib on outcomes of chronic lymphocytic leukemia patients in routine clinical practice

被引：41

作者：

Parikh, Sameer A. ^{[1
]}

Achenbach, Sara J. ^{[2
]}

Call, Timothy G. ^{[1
]}

Rabe, Kari G. ^{[2
]}

Ding, Wei ^{[1
]}

Leis, Jose F. ^{[3
]}

Kenderian, Saad S. ^{[1
]}

Chanan-Khan, Asher A. ^{[4
]}

Koehler, Amber B. ^{[1
]}

Schwager, Susan M. ^{[1
]}

Muchtar, Eli ^{[1
]}

Fonder, Amie L. ^{[1
]}

McCullough, Kristen B. ^{[5
]}

Nedved, Adrienne N. ^{[5
]}

Smith, Matthew D. ^{[5
]}

Slager, Susan L. ^{[2
]}

Kay, Neil E. ^{[1
]}

Finnes, Heidi D. ^{[5
]}

Shanafelt, Tait D. ^{[6
]}

机构：

[1] Mayo Clin, Div Hematol, Dept Med, 200 First St SW, Rochester, MN 55905 USA

[2] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA

[3] Mayo Clin, Dept Hematol & Oncol, Phoenix, AZ USA

[4] Mayo Clin, Div Hematol & Oncol, Jacksonville, FL 32224 USA

[5] Mayo Clin, Dept Pharm, Rochester, MN 55905 USA

[6] Stanford Univ, Sch Med, Div Hematol, Palo Alto, CA 94304 USA

来源：

CANCER MEDICINE | 2020年 / 9卷 / 10期

关键词：

VENETOCLAX; THERAPY; COHORT; CLL;

D O I：

10.1002/cam4.2998

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：3390 / 3399

页数：10

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