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Blood:表观遗传修饰剂联合应用可有效治疗外周T细胞淋巴瘤

2019-09-02 QQ MedSci原创

外周T细胞淋巴瘤(PTCL)对表观遗传修饰因子具有独特的敏感性。根据组蛋白去乙酰化酶(HDAC)抑制剂与低甲基化剂在预临床PTCL模型中的协同作用,研究人员开展一1期试验,明确晚期淋巴恶性肿瘤特别是PTCL)患者(口服5-氮杂胞苷(AZA)和罗米地辛(ROMI)的最大耐受剂量和安全性。本试验采用3+3设计,共有7个队列,AZA的剂量范围:100 mg/天 1-14天-300 mg/天 1-21天,

外周T细胞淋巴瘤(PTCL)对表观遗传修饰因子具有独特的敏感性。根据组蛋白去乙酰化酶(HDAC)抑制剂与低甲基化剂在预临床PTCL模型中的协同作用,研究人员开展一1期试验,明确晚期淋巴恶性肿瘤特别是PTCL)患者(口服5-氮杂胞苷(AZA)和罗米地辛(ROMI)的最大耐受剂量和安全性。

本试验采用3+3设计,共有7个队列,AZA的剂量范围:100 mg/天 1-14天-300 mg/天 1-21天,ROMI的剂量范围:10 mg/m2 第8和15天-14 mg/m2 第8、15和22天,21-35天为一疗程。主要结点有最大耐受剂量(MTD)和剂量限制性毒性(DLT)。

共招募了31位患者。AZA的MTD是1-14天 300 mg/天,ROMI的MTD是第8、15和22天 14 mg/m2,两者都是35天一疗程。DLT包括4级血小板减少、延长的3级血小板减少、4级中性粒细胞减少和胸腔积液。无治疗相关的死亡。

相比于非T细胞淋巴瘤,这种联合疗法对于PTCL患者更有效。所有患者、非T细胞淋巴瘤患者和T细胞淋巴瘤患者的总体缓解率分别是23%、5%和55%。

研究人员未发现缓解与去甲基化水平或肿瘤突变谱之间存在关联。本研究表明表观遗传修饰剂联合应用可有效用于PTCL患者。

原始出处:

Owen A O'Connor,et al.ORAL 5-AZACYTIDINE AND ROMIDEPSIN EXHIBIT MARKED ACTIVITY IN PATIENTS WITH PTCL: A MULTICENTER PHASE I STUDY.Blood 2019 :blood.2019001285; doi: https://doi.org/10.1182/blood.2019001285

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    2019-09-04 zhangyxzsh
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    2019-09-02 orangesking

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