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The New Landscape of Therapy for Myelofibrosis

  • Myeloproliferative Disorders (JJ Kiladjian, Section Editor)
  • Published:
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Abstract

The landscape of therapy for myelofibrosis (MF) is evolving at a pace not previously seen for this clonal myeloproliferative neoplasm. The discovery of the JAK2 V617F mutation in 2005 has led to the rapid development of therapy specifically developed for afflicted MF patients. Indeed, the successful phase III studies of ruxolitinib demonstrating improved symptomatic burden, splenomegaly and survival led to the first approved myelofibrosis drug in the United States and Europe. Multiple additional JAK2 inhibitors are currently in or nearing phase III testing, including SAR302503 (fedratinib), SB1518 (pacritinib) and CYT387 (momelotinib), seeking to offer incremental benefits to ruxolitinib in regards to cytopenias or other disease features. In parallel, phase III testing of pomalidomide is ongoing, with the goal of solidifying the role of immunomodulatory therapy in MF-associated anemia. Multiple single agents strategies are ongoing with histone deacetylase inhibitors, hedgehog inhibitors and hypomethylation agents. Incremental advances are further sought, either in additive or synergistic fashion, from combination strategies of ruxolitinib with multiple different approaches ranging from allogeneic stem cell transplant to current therapies mitigating anemia and further impacting the bone marrow microenvironment or histology. Transitioning from a pre-2011 era devoid of approved MF therapies to one of multiple agents that target not only disease course but symptomatic burden has indeed changed the platform from which MF providers are able to launch individualized treatment plans. In this article, we discuss the diagnostic and therapeutic milestones achieved through MF research and review the emerging pharmacologic agents on the treatment horizon.

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Conflict of Interest

Krisstina Gowin, Robyn Emanuel, and Holly Geyer declare that they have no conflict of interest.

Ruben A. Mesa has received payment for consulting from Novartis, and research support from Sanofi, Incyte, Genentech, Lilly, Gilead, CTI, and Celgene.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Mayo Clinic Cancer Center, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA

    Krisstina Gowin & Ruben A. Mesa

  2. Internal Medicine Residency Program, Mayo Clinic, Scottsdale, AZ, USA

    Robyn Emanuel

  3. Division of Hospital Internal Medicine, Mayo Clinic, Scottsdale, AZ, USA

    Holly Geyer

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  1. Krisstina Gowin
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  2. Robyn Emanuel
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Correspondence to Ruben A. Mesa.

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Gowin, K., Emanuel, R., Geyer, H. et al. The New Landscape of Therapy for Myelofibrosis. Curr Hematol Malig Rep 8, 325–332 (2013). https://doi.org/10.1007/s11899-013-0178-x

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