Multicenter phase 2 study of combination therapy with ruxolitinib and danazol in patients with myelofibrosis. (September 2017)

• Record Type: Journal Article
• Authors: Gowin, K.; Kosiorek, H.; Dueck, A.; Mascarenhas, J.; Hoffman, R.; Reeder, C.; Camoriano, J.; Tibes, R.; Gano, K.; Palmer, J.; Mesa, R.
• Is Part Of: Leukemia research. Volume 60(2017:Sep.)
• Page Start: 31
• Page End: 35
• Publication Date: 2017-09
• Subjects: Myelofibrosis -- Ruxolitinib -- Danazol -- Cytopenias; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2017.06.005
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: Ruxolitinib associated cytopenias often limit tolerance to therapy. Ruxolitinib and danazol therapy demonstrated hematologic stabilization. Combination therapy did not improve response per IWG-MRT criteria. Therapy was generally well tolerated. Combination therapy may be useful in heavily pretreated MF patients. Abstract: 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.