Perspectives on a new therapeutic approach for myeloproliferative neoplasms

Abstract

After the discovery of driver mutations for myeloproliferative neoplasms (MPN), treatment approach for the disease has achieved tremendous progress. Ruxolitinib, a JAK inhibitor, is now widely used for both patients with myelofibrosis and polycythemia vera in several countries, including Japan. Fedratinib, another JAK inhibitor, has been recently approved in the United States. One of the biggest limitations of treatment with JAK inhibitors is the relatively small proportion of patients who achieve a complete molecular response. Furthermore, most of the patients with myelofibrosis had to discontinue the treatment due to drug-related adverse events or disease progression. Therefore, MPN treatment is still at an early and challenging stage, thereby highlighting the urgent need for establishment of a new and more effective therapeutic strategy. One of the promising candidates for MPN treatment is the use of interferons. Modern forms of interferons demonstrate not only a good hematological response but also a deep molecular response, eradicating abnormal MPN clones harboring driver mutations. A number of new agents targeting molecules outside of the JAK-STAT pathway, PI3kinase, NF-kB, or Bcl-2 family of anti-apoptotic proteins are also being considered and tested in clinical studies as single-agent therapies or in combination with JAK inhibitors.