Sastow Dahniel, Tremblay Douglas
Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ther Clin Risk Manag. 2023 Jun 28;19:535-547. doi: 10.2147/TCRM.S386802. eCollection 2023.
Myelofibrosis (MF) is a hematologic malignancy characterized by abnormal proliferation of myeloid cells and the release of pro-inflammatory cytokines, leading to progressive bone marrow dysfunction. The introduction of ruxolitinib just over a decade ago marked a significant advancement in MF therapy, with JAK inhibitors now being the first-line treatment for reducing spleen size and managing symptoms. However, early JAK inhibitors (ruxolitinib and fedratinib) are often associated with cytopenias, particularly thrombocytopenia and anemia, which limit their tolerability. To address these complications, pacritinib has been developed and recently approved for patients with thrombocytopenia, while momelotinib is in development for those with anemia. Although JAK inhibitors have significantly improved the quality of life of MF patients, they have not demonstrated the ability to reduce leukemic transformation and their impact on survival is debated. Numerous drugs are currently being developed and investigated in clinical trials, both as standalone therapy and in combination with JAK inhibitors, with promising results enhancing the benefits of JAK inhibitors. In the near future, MF treatment strategies will involve selecting the most suitable JAK inhibitor based on individual patient characteristics and prior therapy. Ongoing and future clinical trials are crucial for advancing the field and expanding therapeutic options for MF patients.
骨髓纤维化（MF）是一种血液系统恶性肿瘤，其特征为髓系细胞异常增殖和促炎细胞因子释放，导致进行性骨髓功能障碍。就在十多年前，芦可替尼的问世标志着MF治疗取得了重大进展，JAK抑制剂现已成为缩小脾脏大小和控制症状的一线治疗药物。然而，早期的JAK抑制剂（芦可替尼和非达替尼）常与血细胞减少有关，尤其是血小板减少和贫血，这限制了它们的耐受性。为解决这些并发症，帕西替尼已被研发出来并于近期获批用于治疗血小板减少症患者，而莫美替尼正在研发中用于治疗贫血患者。尽管JAK抑制剂显著改善了MF患者的生活质量，但它们尚未显示出降低白血病转化的能力，其对生存的影响也存在争议。目前有许多药物正在进行临床试验研发和研究，既作为单一疗法，也与JAK抑制剂联合使用，取得了有前景的结果，增强了JAK抑制剂的疗效。在不久的将来，MF治疗策略将包括根据个体患者特征和既往治疗情况选择最合适的JAK抑制剂。正在进行的和未来的临床试验对于推动该领域发展以及为MF患者扩大治疗选择至关重要。
