Tefferi A, Al-Ali H K, Barosi G, Devos T, Gisslinger H, Jiang Q, Kiladjian J-J, Mesa R, Passamonti F, McMullin M F, Ribrag V, Schiller G, Vannucchi A M, Zhou D, Reiser D, Zhong J, Gale R P
Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
Universitätsklinikum Leipzig, Leipzig, Germany.
Leukemia. 2017 Apr;31(4):896-902. doi: 10.1038/leu.2016.300. Epub 2016 Oct 24.
RBC-transfusion dependence is common in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. The objective of this study was to determine the rates of RBC-transfusion independence after therapy with pomalidomide vs placebo in persons with MPN-associated myelofibrosis and RBC-transfusion dependence. Two hundred and fifty-two subjects (intent-to-treat (ITT) population) including 229 subjects confirmed by central review (modified ITT population) were randomly assigned (2:1) to pomalidomide or placebo. Trialists and subjects were blinded to treatment allocation. Primary end point was proportion of subjects achieving RBC-transfusion independence within 6 months. One hundred and fifty-two subjects received pomalidomide and 77 placebo. Response rates were 16% (95% confidence interval (CI), 11, 23%) vs 16% (8, 26%; P=0.87). Response in the pomalidomide cohort was associated with ⩽4 U RBC/28 days (odds ratio (OR)=3.1; 0.9, 11.1), age ⩽65 (OR=2.3; 0.9, 5.5) and type of MPN-associated myelofibrosis (OR=2.6; 0.7, 9.5). Responses in the placebo cohort were associated with ⩽4 U RBC/28 days (OR=8.6; 0.9, 82.3), white blood cell at randomization >25 × 10/l (OR=4.9; 0.8, 28.9) and interval from diagnosis to randomization >2 years (OR=4.9; 1.1, 21.9). Pomalidomide was associated with increased rates of oedema and neutropenia but these adverse effects were manageable. Pomalidomide and placebo had similar RBC-transfusion-independence response rates in persons with MPN-associated RBC-transfusion dependence.
红细胞输注依赖在骨髓增殖性肿瘤（MPN）相关骨髓纤维化患者中很常见。本研究的目的是确定泊马度胺与安慰剂治疗MPN相关骨髓纤维化且有红细胞输注依赖的患者后红细胞输注独立率。252名受试者（意向性治疗（ITT）人群），包括经中心审查确认的229名受试者（改良ITT人群），被随机分配（2:1）接受泊马度胺或安慰剂治疗。试验者和受试者对治疗分配不知情。主要终点是在6个月内实现红细胞输注独立的受试者比例。152名受试者接受泊马度胺治疗，77名接受安慰剂治疗。缓解率分别为16%（95%置信区间（CI），11，23%）和16%（8，26%；P = 0.87）。泊马度胺组的缓解与每28天输注红细胞≤4单位（比值比（OR）=3.1；0.9，11.1）、年龄≤65岁（OR = 2.3；0.9，5.5）以及MPN相关骨髓纤维化类型（OR = 2.6；0.7，9.5）有关。安慰剂组的缓解与每28天输注红细胞≤4单位（OR = 8.6；0.9，82.3）、随机分组时白细胞>25×10⁹/L（OR = 4.9；0.8，28.9）以及从诊断到随机分组的间隔>2年（OR = 4.9；1.1，21.9）有关。泊马度胺与水肿和中性粒细胞减少发生率增加有关，但这些不良反应是可控的。在MPN相关红细胞输注依赖的患者中，泊马度胺和安慰剂的红细胞输注独立缓解率相似。
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