Senckenberg Institute of Pathology, University of Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
University of Cologne, Cologne, Germany.
J Hematol Oncol. 2018 Mar 15;11(1):42. doi: 10.1186/s13045-018-0585-5.
Myelofibrosis (MF) is a life-shortening complication of myeloproliferative neoplasms associated with ineffective hematopoiesis, splenomegaly, and progressive bone marrow (BM) fibrosis. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib has been shown to improve splenomegaly, symptom burden, and overall survival in patients with intermediate-2 or high-risk MF compared with placebo or best available therapy (BAT).
The effects of ruxolitinib therapy for up to 66 months on BM morphology in 68 patients with advanced MF with variable BM fibrosis grade were compared with those in 192 matching patients treated with BAT. Available trephine biopsies underwent independent, blinded review by three hematopathologists for consensus-based adjudication of grades for reticulin fibrosis, collagen deposition, and osteosclerosis.
Ruxolitinib treatment versus BAT was associated with greater odds of BM fibrosis improvement or stabilization and decreased odds of BM fibrosis worsening based on changes from baseline in reticulin fibrosis grade. Generally, these changes were accompanied by a sustained higher level of individual spleen size reduction and regression of leukoerythroblastosis. Patients with more advanced baseline fibrosis showed lower spleen size response.
The finding that long-term ruxolitinib therapy may reverse or markedly delay BM fibrosis progression in advanced MF suggests that sustained JAK inhibition may be disease-modifying.
INCB18424-251, ClinicalTrials.gov identifier NCT00509899 .
骨髓纤维化（MF）是一种与无效造血、脾肿大和进行性骨髓（BM）纤维化相关的骨髓增生性肿瘤的缩短生命的并发症。口服 Janus 激酶（JAK）1/JAK2 抑制剂芦可替尼已被证明可改善中间 2 或高危 MF 患者的脾肿大、症状负担和总生存期，与安慰剂或最佳可用治疗（BAT）相比。
比较了长达 66 个月的芦可替尼治疗对 68 例不同 BM 纤维化程度晚期 MF 患者 BM 形态的影响与 192 例接受 BAT 治疗的匹配患者的影响。对可获得的环钻活检进行了由三位血液病理学家进行的独立、盲法审查，以对网状纤维纤维化、胶原沉积和骨质硬化的等级进行共识裁决。
与 BAT 相比，芦可替尼治疗与 BM 纤维化改善或稳定的几率增加和 BM 纤维化恶化的几率降低相关，这是基于基线时网状纤维纤维化等级的变化。通常，这些变化伴随着个体脾肿大减少和白细胞红细胞前体消退的持续更高水平。基线纤维化程度较高的患者显示出较低的脾脏大小反应。
长期芦可替尼治疗可能逆转或显著延迟晚期 MF 中 BM 纤维化进展的发现表明，持续的 JAK 抑制可能具有疾病修饰作用。
INCB18424-251，ClinicalTrials.gov 标识符 NCT00509899。
