Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib
Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib
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DOI：
10.1182/bloodadvances.2018030007
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发表时间：
2019-05-14
期刊：
影响因子：
7.5
通讯作者：
Byrd, John C.
中科院分区：
文献类型：
--
作者：
Awan, Farrukh T.;Schuh, Anna;Byrd, John C.
布鲁顿酪氨酸激酶（BTK）抑制剂伊曲替尼可改善慢性淋巴细胞白血病（CLL）患者的结局;然而，一些患者会发生导致停药的不良事件（AE）。Acalabrutinib是一种有效的共价BTK抑制剂，其选择性高于伊曲替尼。我们评估了100 mg acalabrutinib每日两次或200 mg每日一次在因研究者确定的不耐受而停用伊鲁替尼的CLL患者中的安全性和疗效。在33例接受治疗的患者中（61%为男性;中位年龄为64岁;范围为50-82岁），既往伊鲁替尼治疗的中位持续时间为11.6个月（范围为1-62个月）;从伊鲁替尼停药至开始使用acalabrutinib的中位时间为47天（范围为3-331天）。中位19.0个月（范围：0.2-30.6个月）后，23例患者仍接受acalabrutinib治疗; 10例患者停药（疾病进展，n = 4; AE，n = 3）。未发生acalabrutinib剂量降低。在acalabrutinib治疗期间，最常见的AE包括腹泻（58%）、头痛（39%）和咳嗽（33%）。58%的患者发生了3/4级AE，最常见的是中性粒细胞减少症（12%）和血小板减少症（9%）。在61例与不耐受相关的伊匹替尼相关AE中，72%未复发，13%在使用acalabrutinib时以较低级别复发。总缓解率为76%，其中1例完全缓解、19例部分缓解和5例部分缓解伴淋巴细胞增多。在25名缓解者中，未达到中位缓解持续时间。未达到中位无进展生存期（PFS）; 1年PFS为83.4%（95%置信区间，64.5%-92.7%）。Acalabrutinib耐受性良好，在既往对伊布替尼不耐受的患者中有较高的缓解率。
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib improves patient outcomes in chronic lymphocytic leukemia (CLL); however, some patients experience adverse events (AEs) leading to discontinuation. Acalabrutinib is a potent, covalent BTK inhibitor with greater selectivity than ibrutinib. We evaluated the safety and efficacy of 100 mg of acalabrutinib twice daily or 200 mg once daily in patients with CLL who discontinued ibrutinib because of intolerance as determined by the investigators. Among 33 treated patients (61% men; median age, 64 years; range, 50-82 years), median duration of prior ibrutinib treatment was 11.6 months (range, 1-62 months); median time from ibrutinib discontinuation to acalabrutinib start was 47 days (range, 3-331 days). After a median of 19.0 months (range, 0.2-30.6 months), 23 patients remained on acalabrutinib; 10 had discontinued (progressive disease, n = 4; AEs, n = 3). No acalabrutinib dose reductions occurred. During acalabrutinib treatment, the most frequent AEs included diarrhea (58%), headache (39%), and cough (33%). Grade 3/4 AEs occurred in 58%, most commonly neutropenia (12%) and thrombocytopenia (9%). Of 61 ibrutinib-related AEs associated with intolerance, 72% did not recur and 13% recurred at a lower grade with acalabrutinib. Overall response rate was 76%, including 1 complete and 19 partial responses and 5 partial responses with lymphocytosis. Among 25 responders, median duration of response was not reached. Median progression-free survival (PFS) was not reached; 1-year PFS was 83.4% (95% confidence interval, 64.5%-92.7%). Acalabrutinib was well tolerated with a high response rate in patients who were previously intolerant to ibrutinib.