PDF(Pubmed)
Abstract：
Myelofibrosis (MF) is a rare BCR-ABL negative myeloproliferative neoplasm characterized by clonal proliferation of stem cells, with mutations in JAK2, CALR, or MPL genes. MF presents in primary and secondary forms, with common symptoms including splenomegaly, anemia, and thrombocytopenia. Diagnostic criteria involve bone marrow examination and mutation studies. Current treatments are limited, with allogeneic stem cell transplant as the only curative option. Recent FDA approval of Momelotinib (MMB) offers new promise for MF patients with anemia. MMB, a JAK1/2 and ACVR1 inhibitor, effectively reduces spleen size, improves hemoglobin levels, and decreases transfusion dependency. The MOMENTUM trial compared MMB to danazol in JAK inhibitor-treated MF patients with anemia, showing MMB\'s superior symptom relief and transfusion independence rates. Additionally, the SIMPLIFY-1 and SIMPLIFY-2 trials evaluated MMB in JAK inhibitor-naïve and experienced patients, respectively, confirming MMB\'s non-inferiority to ruxolitinib in spleen volume reduction and highlighting its benefits in transfusion requirements. MMB\'s unique dual inhibition mechanism addresses anemia by suppressing hepcidin production, thus enhancing erythropoiesis. These trials collectively suggest MMB as an effective treatment for MF, improving quality of life and offering a survival advantage for patients with anemia. Despite challenges, such as trial design limitations and adverse events, MMB represents a significant advancement in MF management, providing a new therapeutic option for a previously underserved patient population.
摘要：
骨髓纤维化（MF）是一种罕见的BCR-ABL阴性骨髓增殖性肿瘤，其特征是干细胞的克隆性增殖。JAK2，CALR，或MPL基因。MF以主要和次要形式存在，常见症状包括脾肿大，贫血,和血小板减少症.诊断标准包括骨髓检查和突变研究。目前的治疗方法有限，同种异体干细胞移植是唯一的治疗选择。最近FDA批准的Momelotinib（MMB）为患有贫血的MF患者提供了新的希望。MMB,JAK1/2和ACVR1抑制剂，有效地减少脾脏的大小，改善血红蛋白水平，减少输血依赖性。MOMENTUM试验在JAK抑制剂治疗的MF贫血患者中比较了MMB与达那唑，显示MMB优于症状缓解和输血独立率。此外,SIMPLIFY-1和SIMPLIFY-2试验评估了JAK抑制剂初治和有经验患者的MMB，分别,确认MMB在减少脾脏体积方面与鲁索替尼相比具有非劣效性，并强调其在输血需求方面的益处。MMB独特的双重抑制机制通过抑制铁调素的产生来解决贫血，从而增强红细胞生成。这些试验共同建议MMB作为MF的有效治疗方法，提高生活质量，为贫血患者提供生存优势。尽管面临挑战,如试验设计限制和不良事件，MMB代表了MF管理的重大进步，为以前服务不足的患者人群提供了一种新的治疗选择。
