Gowin K, Kosiorek H, Dueck A, Mascarenhas J, Hoffman R, Reeder C, Camoriano J, Tibes R, Gano K, Palmer J, Mesa R
Mayo Clinic Arizona, Department of Hematology, Phoenix, AZ, USA.
Mayo Clinic Arizona, Department of Health Sciences Research, Section of Biostatistics, Phoenix, AZ, USA.
Leuk Res. 2017 Sep;60:31-35. doi: 10.1016/j.leukres.2017.06.005. Epub 2017 Jun 13.
Myelofibrosis is a myeloproliferative neoplasm that is characterized by splenomegaly, profound symptom burden, and cytopenias. JAK inhibitor therapy offers improvements in splenomegaly, symptom burden, and potentially survival; however, cytopenias remain a significant challenge. Danazol has previously demonstrated improvements in myelofibrosis-associated anemia. We conducted a phase II clinical trial evaluating the efficacy and tolerability of combination therapy with ruxolitinib, an oral JAK inhibitor, and danazol. Fourteen intermediate or high-risk MF patients were enrolled at 2 institutions. Responses per IWG-MRT criteria were stable disease in 9 patients (64.2%) clinical improvement in 3 (21.4%) all of which were spleen responses, partial response in 1 (7.1%) and progressive disease in 1 (7.1%). Despite limited IWG-MRT response, stabilization of anemia and thrombocytopenia was demonstrated. In JAK inhibitor naïve patients, 4/5 (80%) had stable or increasing hemoglobin. Of the 9 patients on prior JAK inhibitor, 5 patients (55.5%) and 8 patients (88.9%) had stable or increasing hemoglobin or platelet levels, respectively. Adverse events possibly related included grade 3 or greater hematologic toxicity in ten patients (71.4%) and non-hematologic toxicity in two patients (14.3%). Although combination therapy did not lead to increased hematologic response per IWG-MRT criteria, hematologic stabilization was observed and may be clinically useful.
骨髓纤维化是一种骨髓增殖性肿瘤，其特征为脾肿大、严重的症状负担和血细胞减少。JAK抑制剂疗法可改善脾肿大、症状负担，并可能提高生存率；然而，血细胞减少仍然是一个重大挑战。达那唑此前已证明可改善骨髓纤维化相关贫血。我们进行了一项II期临床试验，评估口服JAK抑制剂鲁索替尼与达那唑联合治疗的疗效和耐受性。在2家机构招募了14例中高危骨髓纤维化患者。根据IWG-MRT标准，9例患者（64.2%）病情稳定，3例患者（21.4%）临床改善，所有这些均为脾脏反应，1例患者（7.1%）部分缓解，1例患者（7.1%）病情进展。尽管IWG-MRT反应有限，但贫血和血小板减少得到了稳定。在未使用过JAK抑制剂的患者中，4/5（80%）的血红蛋白稳定或升高。在之前使用过JAK抑制剂的9例患者中，分别有5例患者（55.5%）和8例患者（88.9%）的血红蛋白或血小板水平稳定或升高。可能相关的不良事件包括10例患者（71.4%）出现3级或更高级别的血液学毒性，2例患者（14.3%）出现非血液学毒性。虽然联合治疗未导致IWG-MRT标准下血液学反应增加，但观察到血液学稳定，可能具有临床应用价值。
