Istituto di Ematologia "Seràgnoli," IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Division of Hematology and Bone Marrow Transplantation, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy.
Cancer. 2021 Aug 1;127(15):2657-2665. doi: 10.1002/cncr.33541. Epub 2021 Apr 1.
After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities.
The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival.
A total of 219 patients (31.2%) discontinued ruxolitinib for ≥14 days and survived for ≥30 days. In 60 patients (27.4%), ruxolitinib was rechallenged for ≥14 days (RUX-again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX-stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack/loss of spleen response was lower in RUX-again patients (P = .004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (P < .001) and a high Total Symptom Score (TSS; P < .001). During the rechallenge, 44.6% and 48.3% of the patients had spleen and symptom improvements, respectively, with a significant increase in the number of patients with a TSS reduction (P = .01). Although the use of a ruxolitinib dose > 10 mg twice daily predicted better spleen (P = .05) and symptom improvements (P = .02), the reasons for/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX-again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX-again patients (P = .004).
Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities.
鲁索利替尼停药后，骨髓纤维化（MF）患者的预后较差，治疗选择有限。
作者对一项观察性、回顾性研究（RUX-MF）进行了亚分析，该研究纳入了 703 例接受鲁索利替尼治疗的 MF 患者，旨在研究：1）鲁索利替尼再次用药的频率和原因；2）其治疗效果；3）对总生存的影响。
共有 219 例（31.2%）患者因至少 14 天的停药且存活时间至少 30 天而停止使用鲁索利替尼。在 60 例（27.4%）患者中，鲁索利替尼再次用药时间至少 14 天（RUX-again 患者），而 159 例（72.6%）患者则永久性停药（RUX-stop 患者）。两组的基线特征相当，但因脾脏反应缺乏/丧失而停药的 RUX-again 患者比例较低（P=0.004）。与首次鲁索利替尼停药时的疾病状态相比，在重新开始治疗时，大脾脏肿大的患者比例显著增加（P<0.001），总症状评分（TSS）显著升高（P<0.001）。在再次用药期间，分别有 44.6%和 48.3%的患者脾脏和症状改善，TSS 降低的患者数量显著增加（P=0.01）。虽然鲁索利替尼剂量>10 mg 每日 2 次的使用预测脾脏（P=0.05）和症状改善（P=0.02）更好，但停药原因/时间和再次用药前使用其他治疗方法与再次用药疗效无关。在 1 年和 2 年时，分别有 33.3%和 48.3%的 RUX-again 患者永久性停止使用鲁索利替尼。中位总生存时间为 27.9 个月，RUX-again 患者的生存时间显著更长（P=0.004）。
鲁索利替尼再次用药主要用于不耐受的患者；在许多情况下，临床有改善且可能存在生存优势，但永久性停药的比例较高。应权衡鲁索利替尼再次用药与新的治疗可能性。
