BACKGROUND After discontinuing ruxolitinib, the outcome of patients with myelofibrosis reportedly has been poor. The authors investigated whether disease characteristics before the receipt of ruxolitinib may predict drug discontinuation in patients with myelofibrosis and whether reasons for drug discontinuation, disease phase at discontinuation, and salvage therapies may influence the outcome. METHODS A centralized electronic clinical database was created in 20 European hematology centers, including clinical and laboratory data for 524 patients who received ruxolitinib for myelofibrosis. RESULTS At 3 years, 40.8% of patients had stopped ruxolitinib. Baseline predictors of drug discontinuation were: intermediate-2-risk/high-risk category (Dynamic International Prognostic Score System), a platelet count <100 ×109 per liter, transfusion dependency, and unfavorable karyotype. At last contact, 268 patients (51.1%) had discontinued therapy, and the median drug exposure was 17.5 months. Fifty patients (18.7%) died while taking ruxolitinib. The reasons for discontinuation in the remaining 218 patients were the lack (22.9%) or loss (11.9%) of a spleen response, ruxolitinib-related adverse events (27.5%), progression to blast phase (23.4%), ruxolitinib-unrelated adverse events (9.2%), and allogeneic transplantation during response (5.1%). The median survival after ruxolitinib was 13.2 months and was significantly better in the 167 patients who discontinued ruxolitinib in chronic phase (27.5 vs 3.9 months for those who discontinued in blast phase; P < .001). No survival differences were observed among patients who discontinued ruxolitinib in chronic phase because of lack of response, loss of response, or ruxolitinib-related adverse events. The use of investigational agents and/or ruxolitinib rechallenge were associated with improved outcome. CONCLUSIONS The survival of patients with myelofibrosis after discontinuation of ruxolitinib is poor, particularly for those who discontinue in blast phase. Salvage therapies can improve outcome, emphasizing the need for novel therapies.

中文翻译：

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鲁索替尼后的生活：218 名骨髓纤维化患者的停药原因、疾病阶段的影响和结果。

背景 在停用鲁索替尼后，据报道骨髓纤维化患者的预后很差。作者调查了接受鲁索替尼之前的疾病特征是否可以预测骨髓纤维化患者的停药，以及停药的原因、停药时的疾病阶段和挽救治疗是否会影响结果。方法 在 20 个欧洲血液学中心创建了一个集中的电子临床数据库，包括 524 名接受鲁索替尼治疗骨髓纤维化的患者的临床和实验室数据。结果 3 年时，40.8% 的患者停止了鲁索替尼。停药的基线预测因素是：中 2 风险/高风险类别（动态国际预后评分系统），血小板计数 <100 × 109/L，输血依赖性和不利的核型。最后一次接触时，268 名患者 (51.1%) 已停止治疗，中位药物暴露时间为 17.5 个月。50 名患者 (18.7%) 在服用鲁索替尼时死亡。其余 218 名患者中止的原因是脾反应缺乏 (22.9%) 或丧失 (11.9%)、鲁索替尼相关不良事件 (27.5%)、进展至急变期 (23.4%)、鲁索替尼无关不良事件事件 (9.2%) 和反应期间的同种异体移植 (5.1%)。鲁索替尼治疗后的中位生存期为 13.2 个月，在慢性期停用 ruxolitinib 的 167 名患者中明显更好（急变期停用的患者为 27.5 个月 vs 3.9 个月；P < .001）。由于缺乏反应、反应丧失或与鲁索替尼相关的不良事件，在慢性期停用鲁索替尼的患者中未观察到生存差异。使用研究药物和/或鲁索替尼再激发与改善结果相关。结论 停用鲁索替尼后骨髓纤维化患者的生存率很差，尤其是那些在急变期停药的患者。抢救疗法可以改善结果，强调对新疗法的需求。