Ibrutinib plus Venetoclax for the Treatment of Mantle-Cell Lymphoma
Ibrutinib plus Venetoclax for the Treatment of Mantle-Cell Lymphoma
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DOI：
10.1056/nejmoa1715519
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发表时间：
2018-03-29
影响因子：
158.5
通讯作者：
Roberts, Andrew W.
中科院分区：
文献类型：
--
作者：
Tam, Constantine S.;Anderson, Mary Ann;Roberts, Andrew W.
BTK抑制剂伊曲替尼和BCL 2抑制剂维奈托克作为单一疗法治疗套细胞淋巴瘤都很有效。当作为长期连续治疗给药时，观察到每种药物的完全缓解率为21%。临床前模型预测协同combination.METHODSWe进行了单组，每日口服伊替尼和维奈托克患者的2期研究，与历史对照。患者以560 mg/天的剂量开始伊布替尼单药治疗。4周后，逐步添加维奈托克，每周增加剂量至400 mg/天。这两种药物都持续使用，直到疾病进展或不良事件达到不可接受的水平。主要终点是第16周的完全缓解率。通过骨髓流式细胞术和血液等位基因特异性寡核苷酸聚合酶链反应（ASO-PCR）评估微小残留病（MRD）。患者年龄在47至81岁之间，既往治疗次数从零到六次不等。一半的患者有TP 53畸变，75%的患者有高风险预后评分。根据第16周的计算机断层扫描，完全缓解率为42%，高于伊曲替尼单药治疗在该时间点的历史结果9%（P
BACKGROUNDBoth the BTK inhibitor ibrutinib and the BCL2 inhibitor venetoclax are active as monotherapy in the treatment of mantle-cell lymphoma. Complete response rates of 21% have been observed for each agent when administered as long-term continuous therapy. Preclinical models predict synergy in combination.METHODSWe conducted a single-group, phase 2 study of daily oral ibrutinib and venetoclax in patients, as compared with historical controls. Patients commenced ibrutinib monotherapy at a dose of 560 mg per day. After 4 weeks, venetoclax was added in stepwise, weekly increasing doses to 400 mg per day. Both drugs were continued until progression or an unacceptable level of adverse events. The primary end point was the rate of complete response at week 16. Minimal residual disease (MRD) was assessed by flow cytometry in bone marrow and by allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) in blood.RESULTSThe study included 24 patients with relapsed or refractory mantle-cell lymphoma (23 patients) or previously untreated mantle-cell lymphoma (1 patient). Patients were 47 to 81 years of age, and the number of previous treatments ranged from none to six. Half the patients had aberrations of TP53, and 75% had a high-risk prognostic score. The complete response rate according to computed tomography at week 16 was 42%, which was higher than the historical result of 9% at this time point with ibrutinib monotherapy (P