Vnitr Lek 2014, 60(2):158-163

The place of JAK2 inhibitors in the treatment of myelofibrosis. An amendment to the recommendations for diagnosis and treatment of Ph negative myeloproliferations of the Czech group for Ph- myeloproliferative disorders (CZEMP)

Libor Červinek^1,*, Michael Doubek¹, Miroslav Penka², Jiří Schwarz³

¹ Interní hematologická a onkologická klinika LF MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Mayer, CSc.

² Oddělení klinické hematologie FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Miroslav Penka, CSc.

³ Ústav hematologie a krevní transfuze, Praha, ředitel prof. MUDr. Petr Cetkovský, Ph.D., MBA

Primary myelofibrosis (PMF) belongs to Ph- myeloproliferative diseases. The only curative treatment is hematopoietic stem cell transplantation (HSCT). Conservative treatment options comprise supportive care, especially administration of red blood cell and platelet transfusions, and medication. Hydroxyurea, interferon α, anagrelide, corticosteroids, androgens, or inhibitors of angiogenesis (thalidomide, lenalidomide, pomalidomide) may be used for treatment of PMF, depending on the clinical stage and disease symptoms present. Also splenectomy or radiotherapy of enlarged spleen have palliative potential. JAK2 kinase inhibitors represent a novel class of drugs with a very dynamic development. Ruxolitinib, an oral selective inhibitor of JAK1 and JAK2 kinases, has shown high efficacy in patients with high-risk PMF (or with myelofibrosis following polycythemia vera or essential thrombocythemia) to ameliorate disease symptoms and to reduce splenomegaly in randomized trials COMFORT-I and COMFORT-II. Long-term monitoring of the enrolled patients demonstated prolongation of overall survival. The drug is well-tolerated, the most common side effects of treatment with ruxolitinib being deepening of thrombocytopenia and temporary worsening of anemia. The current review deals with the place of JAK2 inhibitors (and the only drug already approved for clinical use - ruxolitinib) in the management of PMF, as an addendum to the Summary of recommendations for the diagnosis and therapy of BCR/ABL-negative myeloproliferations of the Czech Hematological Society's CZEMP.

Keywords: JAK2 inhibitors; ruxolitinib; Ph-negative myeloproliferative diseases; myeloproliferative diseases, myeloproliferative neoplasia; primary myelofibrosis; treatment recommendations

Received: November 25, 2013; Published: February 1, 2014  Show citation