在复发和/或难治性B细胞恶性肿瘤中延长帕托布替尼暴露期的安全性。

IF 1.7 4区 医学 Q3 HEMATOLOGY
Lindsey E Roeker, Catherine C Coombs, Nirav N Shah, Wojciech Jurczak, Jennifer A Woyach, Chan Y Cheah, Krish Patel, Kami Maddocks, Yucai Wang, Pier Luigi Zinzani, Talha Munir, Youngil Koh, Meghan C Thompson, Catherine E Muehlenbein, Chunxiao Wang, Richard Sizelove, Sarang Abhyankar, Safarulla Hasanabba, Donald E Tsai, Toby A Eyre, Michael Wang
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引用次数: 0

摘要

简介皮罗替尼是一种高选择性、非共价(可逆)布鲁顿酪氨酸激酶抑制剂,在B细胞恶性肿瘤中显示出良好的疗效,且停药率和剂量减少率较低。方法:在此,我们报告了BRUIN试验中延长用药时间(≥12个月)的复发/难治性B细胞恶性肿瘤患者服用吡咯替尼的安全性。评估内容包括不良事件(AEs)的中位首次发生时间、剂量减少以及因治疗突发AEs(TEAEs)和特定相关AEs(AESIs)导致的停药:在773名入选患者中,326人(42%)接受了≥12个月的治疗。在暴露时间延长的队列中,治疗时间的中位数为 19 个月。最常见的全因 TEAE 为疲劳(32%)和腹泻(31%)。有 23 例(7%)患者因出现 TEAE 而减少剂量,有 11 例(3%)长期暴露患者因出现 TEAE 而停药。一名患者发生了致命的治疗相关 AE(COVID-19 肺炎)。感染(73.0%)是最常见的 AESI,首次发生的中位时间为 7.4 个月。大多数TEAEs和AESI发生在治疗的第一年:结论:Pirtobrutinib疗法继续表现出良好的安全性,适合长期用药,没有出现新的或恶化的毒性信号。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Safety of Extended Pirtobrutinib Exposure in Relapsed and/or Refractory B-Cell Malignancies.

Introduction: Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment.

Methods: Here we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs).

Results: Of 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy.

Conclusions: Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.

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来源期刊
Acta Haematologica
Acta Haematologica 医学-血液学
CiteScore
4.90
自引率
0.00%
发文量
61
审稿时长
6-12 weeks
期刊介绍: ''Acta Haematologica'' is a well-established and internationally recognized clinically-oriented journal featuring balanced, wide-ranging coverage of current hematology research. A wealth of information on such problems as anemia, leukemia, lymphoma, multiple myeloma, hereditary disorders, blood coagulation, growth factors, hematopoiesis and differentiation is contained in first-rate basic and clinical papers some of which are accompanied by editorial comments by eminent experts. These are supplemented by short state-of-the-art communications, reviews and correspondence as well as occasional special issues devoted to ‘hot topics’ in hematology. These will keep the practicing hematologist well informed of the new developments in the field.
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