Novel treatments to tackle myelofibrosis
- 26 October 2018
- journal article
- review article
- Published by Informa UK Limited in Expert Review of Hematology
- Vol. 11 (11), 889-902
- https://doi.org/10.1080/17474086.2018.1536538
Abstract
Introduction: Despite the dramatic progress made in the treatment of patients with myelofibrosis since the introduction of the JAK1/2 inhibitor ruxolitinib, a therapeutic option that can modify the natural history of the disease and prevent evolution to blast-phase is still lacking. Recent investigational treatments including immunomodulatory drugs and histone deacetylase inhibitors benefit some patients but these effects have proven modest at best. Several novel agents do show promising activity in preclinical studies and early-phase clinical trials. We will illustrate a snapshot view of where the management of myelofibrosis is evolving, in an era of personalized medicine and advanced molecular diagnostics. Areas covered: A literature search using MEDLINE and recent meeting abstracts was performed using the keywords below. It focused on therapies in active phases of development based on their scientific and preclinical rationale with the intent to highlight agents that have novel biological effects. Expert commentary: The most mature advances in treatment of myelofibrosis are the development of second-generation JAK1/2 inhibitors and improvements in expanding access to donors for transplantation. In addition, there are efforts to identify drugs that target pathways other than JAK/STAT signaling that might improve the survival of myelofibrosis patients, and limit the need for stem-cell transplantation.Keywords
This publication has 118 references indexed in Scilit:
- Efficacy and safety of pegylated‐interferon α‐2a in myelofibrosis: a study by the FIM and GEM French cooperative groupsBritish Journal of Haematology, 2013
- Mutations and prognosis in primary myelofibrosisLeukemia, 2013
- JAK2 p.V617F allele burden in myeloproliferative neoplasms one month after allogeneic stem cell transplantation significantly predicts outcome and risk of relapseHaematologica, 2013
- Combination treatment in vitro with Nutlin, a small-molecule antagonist of MDM2, and pegylated interferon-α 2a specifically targets JAK2V617F-positive polycythemia vera cellsBlood, 2012
- The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantationPublished by American Society of Hematology ,2012
- JAK2V617F negatively regulates p53 stabilization by enhancing MDM2 via La expression in myeloproliferative neoplasmsOncogene, 2011
- Selective inhibition of BET bromodomainsNature, 2010
- JAK2-V617F–triggered preemptive and salvage adoptive immunotherapy with donor-lymphocyte infusion in patients with myelofibrosis after allogeneic stem cell transplantationBlood, 2009
- Hematopoietic Cell Transplantation as Curative Therapy for Idiopathic Myelofibrosis, Advanced Polycythemia Vera, and Essential ThrombocythemiaTransplantation and Cellular Therapy, 2007
- Polymorphonuclear Neutrophil and Megakaryocyte Mutual Involvement in Myelofibrosis PathogenesisLeukemia & Lymphoma, 2002