Dexter Tania, Anthias Chloe, Nicholson Emma
Department of Haemato-Oncology, Royal Marsden Hospital, London, UK.
Anthony Nolan, London, UK.
Immunotherapy. 2025 Apr;17(6):409-418. doi: 10.1080/1750743X.2025.2501928. Epub 2025 May 8.
Allogeneic stem cell transplantation represents the only curative option for many patients with high risk hematological malignancies but is associated with a number of severe complications. Of these, chronic graft versus host disease (cGVHD) is the leading cause of late non-relapse mortality and of much morbidity. For over 30 years, glucocorticoids have been the mainstay of first line therapy, yet approximately 50% patients are refractory or dependent and traditionally there have been few options for these patients. In recent years, newer treatments including ruxolitinib and belumosudil have shown success in the second and third line settings. However, further effective nontoxic treatments are a necessary to address this complex debilitating disease. Axatilimab is an antibody to colony stimulating factor 1 (CSF-1), a tyrosine kinase receptor. CSF1R signaling dependent macrophages and monocytes are key mediators of inflammation and fibrosis in chronic GVHD, and thus, this therapy offers a targeted approach. Here we summarize the key clinical studies that have been performed to date of this novel therapy.
异基因干细胞移植是许多高危血液系统恶性肿瘤患者唯一的治愈选择,但会引发多种严重并发症。其中,慢性移植物抗宿主病(cGVHD)是晚期非复发死亡率和高发病率的主要原因。30多年来,糖皮质激素一直是一线治疗的主要药物,但约50%的患者难治或依赖,传统上这些患者的治疗选择很少。近年来,包括芦可替尼和贝莫司他在内的新疗法在二线和三线治疗中取得了成功。然而,需要进一步有效的无毒治疗来应对这种复杂的致残性疾病。阿沙替利单抗是一种针对集落刺激因子1(CSF-1,一种酪氨酸激酶受体)的抗体。CSF1R信号依赖的巨噬细胞和单核细胞是慢性移植物抗宿主病炎症和纤维化的关键介质,因此,这种疗法提供了一种靶向治疗方法。在此,我们总结了迄今为止针对这种新疗法进行的关键临床研究。