Department of Leukemia, University of Texas MD Anderson Cancer Center, 1400 Holcombe Blvd, FC4.3062, Unit 428, Houston, TX, 77030, USA.
Curr Hematol Malig Rep. 2018 Jun;13(3):164-172. doi: 10.1007/s11899-018-0447-9.
Cytopenias, particularly anemia, are frequently encountered in patients with myelofibrosis. Management of cytopenias in myelofibrosis can be very challenging because current therapeutic interventions are only of modest efficacy and ruxolitinib, the only approved drug for myelofibrosis, is myelosuppressive. Yet, dose optimization of ruxolitinib is important for its survival benefit in patients with advanced disease. We sought to summarize the data on treatments for cytopenias available at present and review promising agents in development and emerging strategies.
The activin receptor ligand traps hold considerable promise for the treatment of anemia and could represent an attractive combination strategy with ruxolitinib. Low-dose thalidomide, which could offset both anemia and thrombocytopenia caused by ruxolitinib, represents another potential partner for ruxolitinib. The anti-fibrotic agent PRM-151 produced sustained improvements in cytopenias in some patients, and further data on this drug are eagerly awaited. Finally, several preclinical leads with translational potential are worthy of clinical investigation as strategies to halt/reverse bone marrow fibrosis and thereby improve cytopenias. Cytopenias remain a significant hurdle in myelofibrosis management, but several novel investigational agents hold considerable promise for the future.
骨髓纤维化患者常出现细胞减少症，尤其是贫血。骨髓纤维化患者细胞减少症的治疗极具挑战性，因为目前的治疗干预措施疗效有限，而鲁索利替尼是唯一获批用于骨髓纤维化的药物，具有骨髓抑制作用。然而，鲁索利替尼的剂量优化对于晚期疾病患者的生存获益非常重要。我们旨在总结目前可用于治疗细胞减少症的治疗数据，并综述正在开发和新兴的有前途的药物及治疗策略。
激活素受体配体陷阱在治疗贫血方面具有很大的潜力，可能是与鲁索利替尼联合应用的有吸引力的策略。低剂量沙利度胺可能会抵消鲁索利替尼引起的贫血和血小板减少，这是鲁索利替尼的另一种潜在联合用药。抗纤维化药物 PRM-151 在一些患者中使细胞减少症持续得到改善，人们急切地等待着该药的进一步数据。最后，一些具有转化潜力的临床前研究结果值得进行临床研究，以作为阻止/逆转骨髓纤维化并改善细胞减少症的策略。细胞减少症仍然是骨髓纤维化治疗的一个重大障碍，但一些新的研究药物为未来提供了很大的希望。
