Ten years after ruxolitinib approval for myelofibrosis: a review of clinical efficacy

Abstract

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by splenomegaly, abnormal cytokine expression, cytopenias, and progressive bone marrow fibrosis. The disease often manifests with burdensome symptoms and is associated with reduced survival. Ruxolitinib, an oral Janus kinase (JAK) 1 and JAK2 inhibitor, was the first agent approved for MF. As a first-in-class targeted treatment, ruxolitinib approval transformed the MF treatment approach and remains standard of care. In addition, targeted inhibition of JAK1/JAK2 signaling, a key molecular pathway underlying MF pathogenesis, and the large volume of literature evaluating ruxolitinib, have led to a better understanding of the disease and improved management in general. Here we review ruxolitinib efficacy in patients with MF in the 10 years following approval, including demonstration of clinical benefit in the phase 3 COMFORT-I/II trials, real-world evidence, translational studies, and expanded access data. Lastly, future directions for MF treatment are discussed, including ruxolitinib-based combination therapies.

Keywords:

• Myelofibrosis
• ruxolitinib
• myeloproliferative neoplasm
• Janus kinase

Disclosure statement

Naveen Pemmaraju: Board of directors/management for Dan’s House of Hope. Consultant for AbbVie, Astellas Pharma US, Inc., Cimeio Therapeutics AG, CTI BioPharma, Immunogen, Intellisphere, LLC., Patient Power, PharmaEssentia, Protagonist Therapeutics, and Total CME. Scientific/advisory committee member for Blueprint Medicines, Cancer.Net, CareDx, CTI BioPharma, Incyte, Menarini Group, and Pacylex. Speaker/preceptorship with AbbVie, Aplastic Anemia & MDS International Foundation, Curio Science LLC, Dava Oncology, Intellisphere, LLC., Magdalen Medical Publishing, Medscape, Novartis Pharmaceuticals Corp, Physicians Education Resource, Protagonist Therapeutics, and Targeted Oncology. Research support from US Department of Defense (DOD).

Prithviraj Bose: Research support from Incyte, BMS, CTI, Morphosys, Kartos, Blueprint, Cogent, Astellas, Pfizer, NS Pharma, Promedior, Disk Medicine, Ionis, and Telios. Honoraria from Incyte, BMS, CTI, Sierra (now GSK), Blueprint, Cogent, Novartis, Karyopharm, AbbVie, Pharma Essentia, Morphosys, and Kartos.

Raajit Rampal: Consulting fees from Incyte, Celgene/BMS, Blueprint, AbbVie, Promedior, CTI, Stemline, Galecto, Pharmaessentia, Protagonist, Constellation/Morphosys, Novartis, Sierra Oncology/GSK, and Servier. Research funding from Constellation Pharmaceuticals, Incyte, Zentalis, and Stemline Therapeutics.

Aaron Gerds: Consulting or advisory role with Incyte, AstraZeneca/MedImmune, CTI, Apexx Oncology, and Celgene; received research funding from Pfizer, CTI, Incyte Corporation, Roche/Genentech, Gilead Sciences, Imago Biosciences, Sierra Oncology, and Celgene; equity ownership in Samus Therapeutics.

Angela Fleischman: Speakers bureau for CTI BioPharma and Bristol Myers Squibb, speakers bureau and consultation for PharmaEssentia, and advisory board for Sierra Oncology.

Srdan Verstovsek: Research support from Incyte, Roche, NS Pharma, Celgene, Gilead, Promedior, CTI BioPharma Corp., Genentech, Blueprint Medicines Corp., Novartis, Sierra Oncology, PharmaEssentia, AstraZeneca, Italfarmaco, and Protagonist Therapeutics. Consulting for Constellation, Sierra Oncology, Incyte, Novartis, Celgene, and BMS.

Additional information

Funding

The cost of development of this article and publication fees were funded by Incyte Corporation (Wilmington, DE, USA). Writing assistance was provided by Samantha Locke, PhD, an employee of ICON (Blue Bell, PA, USA), and was funded by Incyte.