关键词: Anemia Anemia supportive therapy Erythropoiesis-stimulating agents Hemoglobin Momelotinib Myelofibrosis Red blood cell transfusions Ruxolitinib Transfusion independence

来  源:   DOI:10.1007/s12325-024-02928-4

Abstract:
BACKGROUND: Some Janus kinase (JAK) inhibitors such as ruxolitinib and fedratinib do not address and may worsen anemia in patients with myelofibrosis. In these cases, the JAK inhibitor may be continued at a reduced dose in an effort to maintain splenic and symptom control, with supportive therapy and/or red blood cell (RBC) transfusions added to manage anemia. This post hoc descriptive analysis of the phase 3 SIMPLIFY-2 trial evaluated the relative benefits of this approach versus switching to the JAK1/JAK2/activin A receptor type 1 inhibitor momelotinib in patients for whom anemia management is a key consideration.
METHODS: SIMPLIFY-2 was a randomized (2:1), open-label, phase 3 trial of momelotinib versus best available therapy (BAT; 88.5% continued ruxolitinib) in JAK inhibitor-experienced patients with myelofibrosis (n = 156). Patient subgroups (n = 105 each) were defined by either baseline (1) hemoglobin (Hb) of < 100 g/L or (2) non-transfusion independence (not meeting the criteria of no transfusions and no Hb of < 80 g/L for the previous 12 weeks); outcomes have been summarized descriptively.
RESULTS: In both subgroups of interest, week 24 transfusion independence rates were higher with momelotinib versus BAT/ruxolitinib: baseline Hb of < 100 g/L, 22 (33.3%) versus 5 (12.8%); baseline non-transfusion independent, 25 (34.7%) versus 1 (3.0%). Mean Hb levels over time were also generally higher in both subgroups with momelotinib, despite median transfusion rates through week 24 with momelotinib being comparable to or lower than with BAT/ruxolitinib. Spleen and symptom response rates with momelotinib in these subgroups were comparable to the intent-to-treat population, while rates with BAT/ruxolitinib were lower.
CONCLUSIONS: In patients with moderate-to-severe anemia and/or in need of RBC transfusions, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using anemia supportive therapies.
BACKGROUND: ClinicalTrials.gov: NCT02101268.
Patients with the rare blood cancer myelofibrosis often experience symptoms such as tiredness, an increase in the size of their spleens (an organ involved in filtering the blood), and anemia (too few red blood cells). One type of treatment for myelofibrosis, called a Janus kinase (JAK) inhibitor, can help patients to feel better and reduce the size of their spleens, but some JAK inhibitors do not help with anemia and may make it worse. In those situations, patients may continue to take their JAK inhibitor but also receive another type of treatment, called an anemia supportive therapy, and may also receive red blood cell transfusions. This study compared 2 treatment approaches, continuing the JAK inhibitor ruxolitinib and adding an anemia supportive therapy and/or transfusions versus switching to another treatment called momelotinib, in 2 groups of patients from a clinical trial: (1) patients with levels of hemoglobin (a red blood cell protein) at the start of the trial that indicated that they had anemia, and (2) patients who were already receiving red blood cell transfusions at the start of the trial. In both groups, more patients did not need red blood cell transfusions anymore at week 24 with momelotinib, and their hemoglobin levels on average became higher over time. More patients also had improvements in spleen size and symptoms with momelotinib. Overall, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using supportive therapies and/or red blood cell transfusions to treat anemia.
摘要:
背景:一些Janus激酶(JAK)抑制剂如鲁索替尼和非司替尼不能解决骨髓纤维化患者的贫血,并可能加重贫血。在这些情况下,JAK抑制剂可以以减少的剂量继续维持脾和症状控制,增加支持治疗和/或红细胞(RBC)输血以控制贫血。这项对3期SIMPLIFY-2试验的事后描述性分析评估了这种方法与转换为JAK1/JAK2/活化素A受体1型抑制剂莫美罗替尼的相对益处。
方法:SIMPLIFY-2是随机的(2:1),开放标签,在患有JAK抑制剂的骨髓纤维化患者(n=156)中,莫美罗替尼与最佳可用疗法(BAT;88.5%继续使用鲁索替尼)的3期试验.患者亚组(每组n=105)定义为基线(1)血红蛋白(Hb)<100g/L或(2)非输血独立性(不符合前12周无输血且无Hb<80g/L的标准);对结果进行了描述性总结。
结果:在两个感兴趣的亚组中,与BAT/ruxolitinib相比,24周输血独立率更高:基线Hb<100g/L,22(33.3%)对5(12.8%);基线非输血独立,25(34.7%)对1(3.0%)。随着时间的推移,莫美罗替尼组的平均Hb水平也普遍较高,尽管莫美罗替尼治疗24周的中位输血率与BAT/ruxolitinib相当或低于BAT/ruxolitinib.在这些亚组中,莫美洛替尼的脾脏和症状反应率与意向治疗人群相当,而BAT/ruxolitinib的比率较低。
结论:中度至重度贫血和/或需要输血的患者,转用莫美罗替尼,而不是继续使用鲁索利替尼和使用贫血支持疗法,结局得到改善.
背景:ClinicalTrials.gov:NCT02101268。
患有罕见血癌骨髓纤维化的患者通常会出现疲倦等症状,它们的脾脏(一个参与过滤血液的器官)的大小增加,贫血(红细胞过少)。骨髓纤维化的一种治疗方法,称为Janus激酶(JAK)抑制剂,可以帮助患者感觉更好,减少脾脏的大小,但是一些JAK抑制剂对贫血没有帮助,可能会使贫血变得更糟。在这种情况下,患者可以继续服用JAK抑制剂,但也可以接受另一种类型的治疗,称为贫血支持疗法,也可能接受红细胞输血。本研究比较了两种治疗方法,继续使用JAK抑制剂ruxolitinib,并增加贫血支持治疗和/或输血,而不是转换为另一种称为莫美罗替尼的治疗,在临床试验的两组患者中:(1)在试验开始时血红蛋白(一种红细胞蛋白)水平表明他们患有贫血的患者,和(2)在试验开始时已经接受红细胞输血的患者。在这两组中,更多的患者在第24周不再需要使用莫美罗替尼进行红细胞输血,随着时间的推移,他们的平均血红蛋白水平变得更高。更多的患者使用莫美罗替尼也改善了脾脏大小和症状。总的来说,转用莫美罗替尼,而不是继续使用鲁索利替尼,并使用支持疗法和/或红细胞输血治疗贫血,结果得到改善.
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