Multicenter phase 2 study of combination therapy with ruxolitinib and danazol in patients with myelofibrosis.

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.

Gowin K ，Kosiorek H ，Dueck A ，Mascarenhas J ，Hoffman R ，Reeder C ，Camoriano J ，Tibes R ，Gano K ，Palmer J ，Mesa R ... -  《-》

[Ruxolitinib combined with prednisone, thalidomide and danazol for treatment of myelofibrosis: a pilot study].

Xu ZF ，Qin TJ ，Zhang HL ，Fang LW ，Pan LJ ，Hu NB ，Qu SQ ，Li B ，Xiao ZJ ... -  《-》

Ruxolitinib combined with prednisone, thalidomide and danazol in patients with myelofibrosis: Results of a pilot study.

Ruxolitinib is a safe and effective therapy of myeloproliferative neoplasm-associated (MPN) myelofibrosis. However, often there are dose reductions and/or therapy interruptions because of therapy-related adverse events (AEs), especially anemia and thrombocytopenia. We previously reported combined therapy with prednisone, thalidomide and danazol (PTD) reversed anemia and thrombocytopenia in people with MPN-associated myelofibrosis. We wondered whether adding PTD to ruxolitinib might mitigate the hematologic AEs and thereby avoid the dose reduction of ruxolitinib and improve the efficacy. To test this hypothesis, we conducted a baseline hemoglobin and platelet concentration assignment prospective observational study in 72 patients comparing 3-month dose adjustment and efficacy of ruxolitinib with (N = 53, the study group) or without (N = 19, the control group) PTD. According to the platelet counts, the median daily ruxolitinib doses in the study group increased from 30 to 40 mg by week 12, whereas in the control group it remained at 30 mg (p = 0.019). In the study group 35 patients had a hemoglobin increase ≥10 g/L compared with no patient receiving ruxolitinib only (p < 0.001). Platelet increases >100 × 10E+9/L were seen in 56.6% and 5.3% of patients in the two groups, respectively (p < 0.001). In patients with anemia and thrombocytopenia, 18 patients in the study group had an anemia response at week 12 and 12 had a platelet increase of ≥50 × 10E+9/L. No patient in the control group achieved either response (p < 0.001 and p = 0.078). The study group had a more spleen response than the control group (p = 0.046). Peripheral edema and transaminase elevation were the main nonhematologic AEs of PTD. These AEs can be alleviated by adjusting the danazol dose. In conclusion, adding PTD to ruxolitinib improved ruxolitinib-associated anemia and thrombocytopenia, and resulted in a higher ruxolitinib dose.

Qu S ，Xu Z ，Qin T ，Li B ，Pan L ，Chen J ，Yan X ，Wu J ，Zhang Y ，Zhang P ，Gale RP ，Xiao Z ... -  《-》

A phase Ib study to assess the efficacy and safety of vismodegib in combination with ruxolitinib in patients with intermediate- or high-risk myelofibrosis.

Couban S ，Benevolo G ，Donnellan W ，Cultrera J ，Koschmieder S ，Verstovsek S ，Hooper G ，Hertig C ，Tandon M ，Dimier N ，Malhi V ，Passamonti F ... -  《-》

Improvement of the hematologic toxicities of ruxolitinib in patients with MPN-associated myelofibrosis using a combination of thalidomide, stanozolol and prednisone.

Duan M ，Zhou D 《-》