Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jul 27;16(1):82.
doi: 10.1186/s13045-023-01471-z.

Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety

Srdan Verstovsek  1 , Ruben A Mesa  2 , Robert A Livingston  3 , Wilson Hu  3 , John Mascarenhas  4
Affiliations
Review

Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety

Srdan Verstovsek et al. J Hematol Oncol. .

Abstract

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Patients with MF are at risk for reduced survival versus the general population and often experience burdensome signs and symptoms that reduce quality of life. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was initially approved by the US Food and Drug Administration in 2011 for the treatment of patients with intermediate or high-risk MF, including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF, based on efficacy and safety findings from the randomized, controlled, phase 3 COMFORT trials. Over a decade later, ruxolitinib continues to be the standard of care in higher-risk MF, and dose optimization and management remain crucial for safely maximizing clinical benefits of ruxolitinib. This review summarizes the safety profile of ruxolitinib in patients with MF in the COMFORT trials leading up to approval and in the subsequent JUMP, ROBUST, EXPAND, and REALISE trials; in pooled analyses; and in postmarketing analyses in the 10 years following approval. There is a focus on the occurrence of common hematologic and nonhematologic adverse events, with guidance provided on the management of patients with anemia or thrombocytopenia, including dosing strategies based on findings from the REALISE and EXPAND trials. Finally, to ensure a greater understanding of the safety profile of ruxolitinib, practical considerations are discussed.

Keywords: Janus kinase; Myelofibrosis; Myeloproliferative neoplasm; Ruxolitinib; Safety.

PubMed Disclaimer

Conflict of interest statement

Srdan Verstovsek received research support from AstraZeneca, Blueprints Medicines Corp., Celgene, CTI BioPharma Corp., Genentech, Gilead, Incyte Corporation, ItalPharma, Novartis, NS Pharma, PharmaEssentia, Promedior, Protagonist Therapeutics, Roche, and Sierra Oncology; and is a paid consultant for Celgene, Incyte, Novartis, and Sierra Oncology. Ruben A. Mesa has served as a consultant for AOP, Incyte, La Jolla Pharma, Novartis, and Sierra; and has received research funding from AbbVie, Celgene, CTI, Genentech, Gilead, Incyte, and Sierra. Robert Livingston and Wilson Hu are employees and shareholders of Incyte. John Mascarenhas received consulting fees from AbbVie, Bristol Myers Squibb, Celgene, Constellation, CTI Bio, Galecto, Geron, GlaxoSmithKline, Incyte, Kartos, Karyopharm, Novartis, PharmaEssentia, Sierra Oncology, and Roche; and research funding paid to the institution from AbbVie, Bristol Myers Squibb, CTI Bio, Geron, Incyte, Kartos, Novartis, PharmaEssentia, and Roche.

Figures

Fig. 1
Fig. 1
JAK signaling in MF and ruxolitinib mechanism of action. BM bone marrow, JAK Janus kinase, MF myelofibrosis, P phosphorylation, STAT signal transducer and activator of transcription
Fig. 2
Fig. 2
Overall survival by anemia status and treatment in the COMFORT trials. Gupta et al. [28]. Reprinted with permission. Copyright (2016) Ferrata Storti Foundation. BL baseline, Rux ruxolitinib
See this image and copyright information in PMC

References

    1. JAKAFI® (ruxolitinib). Full Prescribing Information, Incyte Corporation, Wilmington, DE, USA, 2021.
    1. Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366:787–798. doi: 10.1056/NEJMoa1110556. - DOI - PubMed
    1. Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366:799–807. doi: 10.1056/NEJMoa1110557. - DOI - PMC - PubMed
    1. Verstovsek S, Kiladjian J-J, Vannucchi AM, Mesa RA, Scherber R, Hamer-Maansson JE, et al. Does early intervention in myelofibrosis impact outcomes? A pooled analysis of the COMFORT I and II studies. Blood. 2021;138:1505. doi: 10.1182/blood-2021-150894. - DOI - PubMed
    1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms, version 3.2022. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1477. Accessed November 9, 2022. - PubMed

Publication types