文章：

阿扎胞苷在输血依赖、生长因子耐药、低风险和Int -1风险MDS中的有限临床疗效：来自北欧NMDSG08A II期试验的结果

Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial

原文发布日期：2014-03-07

DOI: 10.1038/bcj.2014.8

类型: Original Article

开放获取: 是

英文摘要：

This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a transfusion need of ⩾4 units over 8 weeks were included. Aza 75 mg m−2 d−1, 5/28 days, was given for six cycles; non-responding patients received another three cycles combined with Epo 60 000 units per week. Primary end point was transfusion independence (TI). All patients underwent targeted mutational screen for 42 candidate genes. Thirty enrolled patients received ⩾one cycle of Aza. Ten patients discontinued the study early, 7 due to adverse events including 2 deaths. Thirty-eight serious adverse events were reported, the most common being infection. Five patients achieved TI after six cycles and one after Aza+Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n=3) and DNMT3A (n=4) were only observed in non-responders. We conclude that Aza can induce TI in severely anemic MDS patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations.

摘要翻译： 

这项前瞻性II期研究评估了阿扎胞苷（Aza）+促红细胞生成素（Epo）在输血依赖型低危骨髓增生异常综合征（MDS）患者中的疗效。研究纳入对足量Epo+粒细胞集落刺激因子治疗超过8周不耐受或无效、且8周内需输注≥4单位血液的患者。患者接受Aza（75 mg·m⁻²·d⁻¹，每28天用药5天）治疗六个周期；无应答者继续接受三个周期联合Epo（每周60,000单位）治疗。主要终点为输血独立性（TI）。所有患者均接受42个候选基因的靶向突变筛查。入组的30例患者均接受至少一个周期Aza治疗，其中10例提前终止研究（7例因不良事件包括2例死亡）。共报告38例严重不良事件，最常见为感染。六个周期后5例患者获得TI，联合治疗后新增1例TI，总应答率为20%。突变筛查显示复发突变频率较高，虽无单一突变可预测应答，但SF3A1（3例）和DNMT3A（4例）突变仅见于无应答者。结论认为：Aza能诱导严重贫血型MDS患者获得TI，但疗效有限、毒性显著且多数应答持续时间短，不推荐常规用于低危MDS治疗。突变筛查提示基因突变频率较高。

原文链接：

Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial