Phase II Study of Flavopiridol in Relapsed Chronic Lymphocytic Leukemia Demonstrating High Response Rates in Genetically High-Risk Disease
Phase II Study of Flavopiridol in Relapsed Chronic Lymphocytic Leukemia Demonstrating High Response Rates in Genetically High-Risk Disease
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DOI：
10.1200/jco.2009.22.6944
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发表时间：
2009-12-10
影响因子：
45.3
通讯作者：
Byrd, John C.
中科院分区：
文献类型：
--
作者：
Lin, Thomas S.;Ruppert, Amy S.;Byrd, John C.
目的慢性淋巴细胞白血病（CLL）患者具有高危基因组特征，传统治疗效果不佳。一项关于flavopiridol药代动力学衍生方案的I期研究表明，无论高危特征如何，其在CLL中具有良好的活性。鉴于这些研究结果的相关性，以治疗遗传高风险的慢性淋巴细胞白血病，一个前瞻性的验证性研究initiated.Patients和MethodsPatients复发慢性淋巴细胞白血病与单药flavopiridol治疗，随后加入地塞米松抑制细胞因子释放综合征（CRS）。高风险的基因组特征进行了前瞻性评估，对therapy. ResultsSixty 4例患者入选。中位年龄为60岁，既往治疗的中位次数为4次，所有患者既往均接受过嘌呤类似物治疗。如果患者在第1周耐受治疗，则在第2周进行剂量递增。由于重度肿瘤溶解综合征，4例患者未发生剂量递增;其中3例患者需要血液透析。34例患者（53%）达到缓解，包括30例部分缓解（PR; 47%），3例结节性PR（5%）和1例完全缓解（1.6%）。大多数高风险患者有反应; 21例del（17p13.1）患者中有12例（57%）和28例del（11q22.3）患者中有14例（50%）有反应，无论淋巴结大小如何。在所有细胞遗传学风险组中，应答者的中位无进展生存期为10至12个月。将每周治疗次数从4次减少到3次，并预防性添加地塞米松，这消除了白细胞介素-6的释放和CRS（P
PurposePatients with chronic lymphocytic leukemia (CLL) with high-risk genomic features achieve poor outcomes with traditional therapies. A phase I study of a pharmacokinetically derived schedule of flavopiridol suggested promising activity in CLL, irrespective of high-risk features. Given the relevance of these findings to treating genetically high-risk CLL, a prospective confirmatory study was initiated.Patients and MethodsPatients with relapsed CLL were treated with single-agent flavopiridol, with subsequent addition of dexamethasone to suppress cytokine release syndrome (CRS). High-risk genomic features were prospectively assessed for response to therapy.ResultsSixty-four patients were enrolled. Median age was 60 years, median number of prior therapies was four, and all patients had received prior purine analog therapy. If patients tolerated treatment during week 1, dose escalation occurred during week 2. Dose escalation did not occur in four patients, as a result of severe tumor lysis syndrome; three of these patients required hemodialysis. Thirty-four patients (53%) achieved response, including 30 partial responses (PRs; 47%), three nodular PRs (5%), and one complete response (1.6%). A majority of high-risk patients responded; 12 (57%) of 21 patients with del(17p13.1) and 14 (50%) of 28 patients with del(11q22.3) responded irrespective of lymph node size. Median progression-free survival among responders was 10 to 12 months across all cytogenetic risk groups. Reducing the number of weekly treatments per cycle from four to three and adding prophylactic dexamethasone, which abrogated interleukin-6 release and CRS (P