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Ruxolitinib in contemporary treatment of myelofibrosis

Ahmed Ahmed, Aylin Kerim, Denica Koleva, Emil Milev

Abstract

Introduction: Myelofibrosis (MF) is a rare chronic Ph(-) myeloproliferative neoplasm that can man­ifest as a primary disease or secondary to polycythaemia vera or essential thrombocythaemia. MF results from dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcrip­tion (STAT) pathway and the most common mutations are JAK2V617F and in the Myeloprolifera­tive leukaemia protein (MLP) gene. For decades, the therapy has been mainly palliative (Immuno­modulators, DNA methyltransferase inhibitors, colony stimulating factors) with none of them lead­ing to complete remission. Ruxolitinib is a new generation JAK1 and JAK2 inhibitor having a remark­able impact on bone marrow fibrosis (BMF) and splenomegaly in patients with high and intermedi­ate-risk MF. The aim of this research is a discussion of the mechanisms of actions of Ruxolitinib and its efficacy

Materials and methods: A documentary approach is used. A targeted analysis of publications, avail­able in PubMed and ScienceDirect is presented. The keywords used to collect the data were: `ruxoli­tinib myelofibrosis` (5 publications); `ruxolitinib mechanisms of actions` (3 publications); `ruxoli­tinib trials` (4 publications).

Results: Ruxolitinib has dose-dependent efficiency on BMF, spleen size and constitutional symp­toms like anaemia, fever and weight loss. Ruxolitinib`s effects are mediated by the following molec­ular mechanisms: a decrease in activation, proliferation and migration of Natural killer and den­dritic cells, a reduction of proinflammatory cytokines like Interleukin-1, Tumor Necrosis Factor-α, Interferon-γ; an increase in plasticity and titre of Th17 cells; stabilization of the serum albumin and total cholesterol that results in weight gain. `Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment` I and `Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment` II are phase III trials which demonstrate how Ruxolitinib makes a reduction of 35% in spleen size and 33% in le­thal exit.

Conclusion: Ruxolitinib is a good example of how targeted therapy ameliorates progression free sur­vival and overall survival.


Keywords

myelofibrosis; ruxolitinib; targeted therapy; oncohaematology




DOI: http://dx.doi.org/10.14748/ssvs.v2i0.4694

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