背景:Ruxolitinib(RUX)是一种JAK1/2抑制剂,基于仅包括中高危(INT2/HIGH)患者的临床试验,被批准用于骨髓纤维化(MF)的治疗。然而,RUX常用于中间-1(INT1)患者,关于回应和结果的信息很少。
方法:作者调查了RUX对1055例MF患者的益处,纳入“RUX-MF”回顾性研究。
结果:在基线(BL),根据DIPSS(PMF)或MYSEC-PM(SMF),595例(56.2%)患者处于INT1风险。脾脏在<5cm处可触及,在5到10厘米之间,肋缘以下>10厘米,占5.9%,47.4%,39.7%的病人,分别为300(54.1%)有高度症状(症状总分≥20)。在77/167例患者中检测到高分子风险(HMR)突变(IDH1/2,ASXL-1,SRSF2,EZH2,U2AF1Q157)。共有101例(19.2%)患者出现≥1次血细胞减少(Hb<10g/dL:n.36;PLT<100x109/L:n=43;白细胞<4x109/L:n=40)。在RUX上6个月后,IWG-MRT定义的脾脏和症状反应率分别为26.8%和67.9%,分别。在单变量分析中,6个月时SR的预测因子为无HMR突变比值比[OR],2.0,p=.05],无血细胞减少症(或,2.10;p=0.01),和爆炸<1%(或,1.91;p=0.01)。在多变量分析中,缺乏HMR保持了显著的关联(OR,2.1[1.12-3.76];p=.01)。
结论:在INT1患者中,反应更加频繁和持久,而与INT2/高危患者相比,毒性发生率较低.HMR突变的存在,血细胞减少,外周母细胞识别出反应较低的INT1患者,谁可能受益于替代治疗策略。
BACKGROUND: Ruxolitinib (RUX) is a JAK1/2 inhibitor approved for the therapy of
myelofibrosis (MF) based on clinical trials including only intermediate2-high risk (INT2/HIGH) patients. However, RUX is commonly used in intermediate-1 (INT1) patients, with scarce information on responses and outcome.
METHODS: The authors investigated the benefit of RUX in 1055 MF patients, included in the \"RUX-MF\" retrospective study.
RESULTS: At baseline (BL), 595 (56.2%) patients were at INT1-risk according to DIPSS (PMF) or MYSEC-PM (SMF). The spleen was palpable at <5 cm, between 5 and 10 cm, and >10 cm below costal margin in 5.9%, 47.4%, and 39.7% of patients, respectively; 300 (54.1%) were highly symptomatic (total symptom score ≥20). High-molecular-risk (HMR) mutations (IDH1/2, ASXL-1, SRSF2, EZH2, U2AF1Q157) were detected in 77/167 patients. A total of 101 (19.2%) patients had ≥1 cytopenia (Hb < 10 g/dL: n.36; PLT <100 x 109/L: n = 43; white blood cells <4 x 109/L: n = 40). After 6 months on RUX, IWG-MRT-defined spleen and symptoms response rates were 26.8% and 67.9%, respectively. In univariate analysis, predictors of SR at 6 months were no HMR mutations odds ratio [OR], 2.0, p = .05], no cytopenia (OR, 2.10; p = .01), and blasts <1% (OR, 1.91; p = .01). In multivariate analysis, absence of HMR maintained a significant association (OR, 2.1 [1.12-3.76]; p = .01).
CONCLUSIONS: In INT1 patients, responses were more frequent and durable, whereas toxicity rates were lower compared to INT2/high-risk patients. Presence of HMR mutations, cytopenia, and peripheral blasts identified less-responsive INT1 patients, who may benefit for alternative therapeutic strategies.