Reduced occurrence of tumor flare with flavopiridol followed by combined flavopiridol and lenalidomide in patients with relapsed chronic lymphocytic leukemia (CLL).
Reduced occurrence of tumor flare with flavopiridol followed by combined flavopiridol and lenalidomide in patients with relapsed chronic lymphocytic leukemia (CLL).
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在复发性慢性淋巴细胞白血病 (CLL) 患者中，使用黄吡醇后联合使用黄吡醇和来那度胺可减少肿瘤复发的发生。
DOI：
10.1002/ajh.23946
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发表时间：
2015
影响因子：
12.8
通讯作者：
Phel
中科院分区：
文献类型：
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作者：
Maddocks,Kami;Wei,Lai;Rozewski,Darlene;Jiang,Yao;Zhao,Yuan;Adusumilli,Mikhil;Pierceall,WilliamE;Doykin,Camille;Cardone,MichaelH;Jones,JeffreyA;Flynn,Joseph;Andritsos,LeslieA;Grever,MichaelR;Byrd,JohnC;Johnson,AmyJ;Phel
氟哌利多和来那度胺在难治性CLL中具有活性，没有免疫抑制或其他疗法所见的机会性感染。我们假设，在来那度胺治疗之前，黄烷醇治疗可以充分消除疾病，减少高剂量来那度胺的肿瘤复发的发生率。在这项I期研究中，用来那度胺每日15 mg口服来那度胺15 mg/次，静脉推注(IVB) + 30 mg/m−，持续静脉输注(C)周期(C)第1天(D)，30 mg/m−2IVB + 50 mg/m−2CIVI C1 D8，15和C2-8 D3，10，17的治疗未达到最大耐受量。没有看到意想不到的毒性，包括没有增加肿瘤溶解，肿瘤红肿(即使在更高剂量的来那度胺)或机会性感染。显示出显著的临床活跃性，在这组接受大量预治疗的患者中，有效率为51%。生物标记物测试证实了BH3唯一多肽Puma的线粒体启动与应答之间的关联。J.血醇。2015年，90：327-333。©2015 Wiley期刊，Inc.
Flavopiridol and lenalidomide have activity in refractory CLL without immunosuppression or opportunistic infections seen with other therapies. We hypothesized that flavopiridol treatment could adequately de‐bulk disease prior to lenalidomide therapy, decreasing the incidence of tumor flare with higher doses of lenalidomide. In this Phase I study, the maximum tolerated dose was not reached with treatment consisting of flavopiridol 30 mg m−2intravenous bolus (IVB) + 30 mg m−2continuous intravenous infusion (CIVI) cycle (C) 1 day (D) 1 and 30 mg m−2IVB + 50 mg m−2CIVI C1 D8,15 and C2‐8 D3,10,17 with lenalidomide 15 mg orally daily C2‐8 D1‐21. There was no unexpected toxicity seen, including no increased tumor lysis, tumor flare (even at higher doses of lenalidomide) or opportunistic infection. Significant clinical activity was demonstrated, with a 51% response rate in this group of heavily pretreated patients. Biomarker testing confirmed association of mitochondrial priming of the BH3 only peptide Puma with response.Am. J. Hematol. 90:327–333, 2015. © 2015 Wiley Periodicals, Inc.