Myelofibrosis is a myeloid neoplasm characterised by the presence of , or mutations (with a 90% mutation frequency) and trilineage myeloid proliferation with prominent megakaryocyte atypia. People with myelofibrosis have a lower survival rate and poorer quality of life than healthy individuals. Therapy for myelofibrosis uses Janus kinase inhibitors, which reduce splenomegaly and alleviate symptoms. Regulatory approvals for Janus kinase inhibitors have focused on this dual endpoint. In this Viewpoint, we discuss the validity of using spleen reduction as a surrogate endpoint for the disease-modifying activity of candidate drugs for myelofibrosis. We suggest alternative endpoints addressing unmet patient needs, including progression-free survival and overall survival. Moreover, we highlight the importance of selecting a core set of crucial outcomes with which we can individualise clinical decision making and standardise reporting of clinical trials results. We propose selecting patient-reported outcomes and anaemia response. We also suggest integrating economic considerations in the process of evaluating new drugs for myelofibrosis.

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制定骨髓纤维化临床试验终点的方法学挑战

骨髓纤维化是一种骨髓肿瘤，其特征是存在 、 或 突变（突变频率为 90%）和三系骨髓增生，并伴有显着的巨核细胞异型性。与健康人相比，骨髓纤维化患者的生存率较低，生活质量也较差。骨髓纤维化治疗使用 Janus 激酶抑制剂，可减少脾肿大并缓解症状。 Janus 激酶抑制剂的监管批准主要集中在这一双重终点上。在本观点中，我们讨论了使用脾脏缩小作为骨髓纤维化候选药物改善疾病活性的替代终点的有效性。我们建议采用替代终点来解决未满足的患者需求，包括无进展生存期和总生存期。此外，我们强调选择一组核心关键结果的重要性，通过这些结果我们可以个性化临床决策并标准化临床试验结果的报告。我们建议选择患者报告的结果和贫血反应。我们还建议在评估骨髓纤维化新药的过程中纳入经济考虑。