Clinical use of ruxolitinib in an academic medical center in unselected patients with myeloproliferative neoplasms not on clinical study

Abstract Ruxolitinib is the only approved therapy for myelofibrosis (MF). However, its use in patients with myeloproliferative neoplasms (MPN) not participating in clinical studies has been poorly described. We reviewed the medical records of 45 patients (35 MF, 10 others) treated with ruxolitinib at our center, off clinical study, during the year after its approval. Patients had advanced features and were refractory to multiple therapies. Ruxolitinib was effective in reducing splenomegaly (51% response rate) and constitutional symptoms (42% response rate). It controlled blood counts in patients with polycythemia and thrombocythemia but was not effective in patients with non-classic MPNs. Ruxolitinib was an active therapy in patients previously treated with a JAK inhibitor and was safely combined with hypomethylating agents in patients with elevated blasts. Median overall survival was 24 months; 10 patients transformed to acute leukemia. Its use in combination with other active agents should be further explored in clinical studies.

[1]  Kuan-Der Lee,et al.  Clinical efficacy and safety of ruxolitinib in the management of myelofibrosis: A single institution experience in Taiwan , 2016, Hematology.

[2]  H. Kantarjian,et al.  Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase. , 2015, Leukemia research.

[3]  N. Lavi,et al.  Ruxolitinib treatment for myelofibrosis: Efficacy and tolerability in routine practice. , 2015, Leukemia research.

[4]  H. Kantarjian,et al.  A phase I/II study of the Janus kinase (JAK)1 and 2 inhibitor ruxolitinib in patients with relapsed or refractory acute myeloid leukemia. , 2015, Clinical lymphoma, myeloma & leukemia.

[5]  Y. Saunthararajah,et al.  Ruxolitinib in combination with DNA methyltransferase inhibitors: clinical responses in patients with symptomatic myelofibrosis with cytopenias and elevated blast(s) counts , 2015, Leukemia & lymphoma.

[6]  C. Harrison,et al.  Combination therapy with ruxolitinib plus 5‐azacytidine or continuous infusion of low dose cytarabine is feasible in patients with blast‐phase myeloproliferative neoplasms , 2014, British journal of haematology.

[7]  R. Hoffman,et al.  Development of extramedullary sites of leukaemia during ruxolitinib therapy for myelofibrosis , 2014, British journal of haematology.

[8]  R. Mesa,et al.  Ruxolitinib in clinical practice for therapy of myelofibrosis: Single USA center experience following Food and Drug Administration approval , 2014, Leukemia & lymphoma.

[9]  Francisco Cervantes,et al.  Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. , 2013, Blood.

[10]  Z. Estrov,et al.  Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. , 2012, Blood.

[11]  Jason Gotlib,et al.  A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. , 2012, The New England journal of medicine.

[12]  Francisco Cervantes,et al.  JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. , 2012, The New England journal of medicine.

[13]  A. Tefferi,et al.  Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  B. Quesnel,et al.  Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). , 2010, Blood.

[15]  M. Cazzola,et al.  Dynamic International Prognostic Scoring System (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis. , 2010, Blood.

[16]  V. Najfeld,et al.  Therapeutic options for patients with myelofibrosis in blast phase. , 2010, Leukemia research.

[17]  R. Mesa,et al.  New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. , 2008, Blood.

[18]  S. Verstovsek,et al.  5-Azacitidine has limited therapeutic activity in myelofibrosis , 2009, Leukemia.

[19]  U. Germing,et al.  The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features , 2008, Leukemia.

[20]  H. Kantarjian,et al.  A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia/polycythemia vera myelofibrosis , 2008, Leukemia.

[21]  P. Campbell,et al.  Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the international working group for myelofibrosis research and treatment , 2008, Leukemia.

[22]  A. Tefferi,et al.  Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms , 2008, Leukemia.

[23]  Stefan N. Constantinescu,et al.  A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera , 2005, Nature.

[24]  P. Wollan,et al.  Population‐based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: An Olmsted county study, 1976–1995 , 1999, American journal of hematology.