Forging ahead or moving back: dilemmas and disappointments of novel agents for myeloproliferative neoplasms

• Published in: British journal of haematology Vol. 191; no. 1; pp. 21 - 36
• Main Authors: McLornan, Donal P., Harrison, Claire N.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.10.2020
• Subjects: Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Hematologic Neoplasms - drug therapy; Hematologic Neoplasms - genetics; Hematologic Neoplasms - metabolism; Hematologic Neoplasms - pathology; Hematology; Humans; Janus kinase; Janus kinase (JAK) inhibitor; Myelofibrosis; Myeloproliferative Disorders - drug therapy; Myeloproliferative Disorders - genetics; Myeloproliferative Disorders - metabolism; Myeloproliferative Disorders - pathology; myeloproliferative neoplasm; novel therapy; Philadelphia chromosome; Quality of Life; Thrombosis; Transcription factors; Tumors; myeloproliferative neoplasm; Janus kinase (JAK) inhibitor; novel therapy
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.16573

Summary The common ‘Philadelphia chromosome’‐negative myeloproliferative neoplasms (MPN) comprise essential thrombocythaemia, polycythaemia vera and myelofibrosis. These are clinically diverse disorders and present many challenges during their course, ranging from the management of very indolent, chronic‐phase disease through to very aggressive stages frequently associated with poor quality of life, heavy symptom burdens and potentially life expectancies of <18 months. Their management also requires expertise in thrombosis and haemostasis in addition to marrow failure, debilitating symptom control and balancing the ‘pros and cons’ of intensive therapy such as allogeneic stem cell transplant versus novel and established therapies. In the past 15 years this field has seen rapid advances following an understanding of the pivotal importance of constitutive Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling, the interplay of the wider genomic landscape and the development of updated diagnostic criteria, prognostic scores and targeted therapies. In this article, we review the successes and failures of novel agents and approaches to MPN management.