Most patients with myelofibrosis (MF) discontinue ruxolitinib (JAK1/JAK2 inhibitor) in the first 5 years of therapy due to therapy failure. As the therapeutic possibilities of MF are expanding, it is critical to identify patients predisposed to early ruxolitinib monotherapy failure and worse outcomes. We investigated predictors of early ruxolitinib discontinuation and death on therapy in 889 patients included in the “RUX-MF” retrospective study. Overall, 172 patients were alive on ruxolitinib after ≥5 years (long-term ruxolitinib, LTR), 115 patients were alive but off ruxolitinib after ≥5 yrs (short-term RUX, STR), and 123 patients died while on ruxolitinib after <5 yrs (early death on ruxolitinib, EDR). The cumulative incidence of the blast phase was similar in LTR and STR patients (p= 0.08). Overall survival (OS) was significantly longer in LTR pts (p= 0.002). In multivariate analysis, PLT < 100 × 109/L, Hb < 10 g/dL, primary MF, absence of spleen response at 3 months and ruxolitinib starting dose <10 mg BID were associated with higher probability of STR. Assigning one point to each significant variable, a prognostic model for STR (STR-PM) was built, and three groups were identified: low (score 0–1), intermediate (score 2), and high risk (score ≥ 3). The STR-PM may identify patients at higher risk of failure with ruxolitinib monotherapy who should be considered for alternative frontline strategies.
大多数骨髓纤维化（MF）患者在治疗的前5年内因治疗失败而停用鲁索替尼（JAK1/JAK2抑制剂）。随着MF治疗方案的不断扩展，识别易发生早期鲁索替尼单药治疗失败及预后较差的患者至关重要。我们在纳入889例患者的“RUX-MF”回顾性研究中，探讨了早期停用鲁索替尼及治疗期间死亡的预测因素。总体而言，172例患者在鲁索替尼治疗≥5年后仍存活（长期鲁索替尼治疗组，LTR），115例患者在≥5年后存活但已停用鲁索替尼（短期鲁索替尼治疗组，STR），123例患者在鲁索替尼治疗<5年内死亡（鲁索替尼治疗早期死亡组，EDR）。LTR与STR患者的急变期累积发生率相似（p=0.08）。LTR患者的总生存期显著更长（p=0.002）。多变量分析显示，血小板计数<100×10⁹/L、血红蛋白<10 g/dL、原发性MF、3个月时无脾脏反应以及鲁索替尼起始剂量<10 mg每日两次与更高的STR发生率相关。通过为每个显著变量分配1分，构建了STR预后模型（STR-PM），并划分出三个风险组：低危（0-1分）、中危（2分）和高危（≥3分）。STR-PM可用于识别鲁索替尼单药治疗失败风险较高的患者，这类患者应考虑采用替代的一线治疗策略。
A Prognostic Model to Predict Ruxolitinib Discontinuation and Death in Patients with Myelofibrosis
肿瘤(癌症)患者之家