Ruxolitinib (RUX) 是一种 JAK1/2 抑制剂，基于仅包括中高风险 (INT2/HIGH) 患者的临床试验，被批准用于治疗骨髓纤维化 (MF)。然而，RUX 通常用于中间 1 (INT1) 患者，有关反应和结果的信息很少。作者调查了 RUX 在 1055 名 MF 患者中的益处，包括在“RUX-MF”回顾性研究中。 ），根据 DIPSS (PMF) 或 MYSEC-PM (SMF)，595 名 (56.2%) 患者处于 INT1 风险。分别有 5.9%、47.4% 和 39.7% 的患者在肋缘以下 <5 cm、5 至 10 cm 和 >10 cm 处可触及脾脏； 300 名（54.1%）有严重症状（总症状评分≥20）。在 77/167 名患者中检测到高分子风险 (HMR) 突变（IDH1/2、ASXL-1、SRSF2、EZH2、U2AF1Q157）。总共 101 名 (19.2%) 患者出现≥1 次血细胞减少（Hb < 10 g/dL：n.36；PLT <100 x 109/L：n = 43；白细胞 <4 x 109/L：n = 40 ）。使用 RUX 6 个月后，IWG-MRT 定义的脾脏和症状缓解率分别为 26.8% 和 67.9%。在单变量分析中，6 个月时 SR 的预测因素是无 HMR 突变比值比 [OR]，2.0，p = .05]、无血细胞减少（OR，2.10；p = .01）和原始细胞 <1%（OR，1.91 p = .01)。在多变量分析中，HMR 的缺失保持了显着关联（OR，2.1 [1.12-3.76]；p = .01）。在 INT1 患者中，反应更频繁、更持久，而与 INT2/高危患者相比，毒性发生率更低患者。 HMR 突变、血细胞减少和外周原始细胞的存在确定了反应较差的 INT1 患者，这些患者可能会受益于替代治疗策略。© 2024 作者。 《癌症》由 Wiley periodicals LLC 代表美国癌症协会出版。

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.The authors investigated the benefit of RUX in 1055 MF patients, included in the "RUX-MF" retrospective study.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).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.© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.