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
. 2022 Jun;36(6):1689-1692.
doi: 10.1038/s41375-022-01544-x. Epub 2022 Mar 26.

Clinical and molecular correlates of JAK-inhibitor therapy failure in myelofibrosis: long-term data from a molecularly annotated cohort

James T England #  1 , Caroline J McNamara #  1 , James A Kennedy  2 , Jose-Mario Capo-Chichi  3 , Jingyue Huang  4 , Andrea Arruda  1 , Taylor Nye  1 , Verna Cheung  1 , Jaime O Claudio  1 , Dawn Maze  1 , Hassan Sibai  1 , Anne Tierens  5 , Hubert Tsui  5 , Aniket Bankar  1 , Wei Xu  4 , Tracy Stockley  3   6 , Vikas Gupta  7
Affiliations

Clinical and molecular correlates of JAK-inhibitor therapy failure in myelofibrosis: long-term data from a molecularly annotated cohort

James T England et al. Leukemia. 2022 Jun.
No abstract available

PubMed Disclaimer

Conflict of interest statement

CM has received honoraria from Novartis. DM has received research support from Novartis, Celgene/Bristol-Myers Squibb, PharmaEssentia, Takeda; honoraria from Novartis, Celgene/Bristol-Myers Squibb; served on the advisory board of Novartis, and provided consultancy for Pfizer. VG received research funding through his institution and honoraria from Novartis and Incyte and has served on the advisory board of Novartis, Incyte, BMS-Celgene, Abb Vie, Sierra Oncology, Pfizer, Takeda, and Constellation Biopharma; The remaining authors stated that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1. Predictors of overall survival following JAKi failure.
Kaplan-Meier survival curve for a DIPSS at the time of JAKi failure, b ECOG at time of failure, c clinical pattern of JAKi failure, and d presence of emergent mutations. Survival curves compared with log rank method.
Fig. 2
Fig. 2. Geneplots for patients treated with JAKi organized by pattern of JAKi failure (x-axis) and mutation category (y-axis).
a Baseline mutations present prior to start of JAKi therapy, with no difference in number or genes mutated between pattern of failure groups. b Geneplot demonstrating n = 55 patients with paired mutation analysis arranged by pattern of failure (n = 49) or ongoing response to JAKi (n = 6). Emergent mutations were more frequently observed in patients with JAKi failure due to AP/BP (n = 7/10) than failure due to cytopenia (n = 1/10, P = 0.006).
See this image and copyright information in PMC

References

    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. Harrison CN, Vannucchi AM, Kiladjian J-J, Al-Ali HK, Gisslinger H, Knoops L, et al. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016;30:1701–7. doi: 10.1038/leu.2016.148. - DOI - PMC - PubMed
    1. Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I. Haematologica. 2015;100:479–88. doi: 10.3324/haematol.2014.115840. - DOI - PMC - PubMed
    1. Kuykendall AT, Shah S, Talati C, Al Ali N, Sweet K, Padron E, et al. Between a rux and a hard place: evaluating salvage treatment and outcomes in myelofibrosis after ruxolitinib discontinuation. Ann Hematol. 2018;97:435–41. doi: 10.1007/s00277-017-3194-4. - DOI - PubMed
    1. Newberry KJ, Patel K, Masarova L, Luthra R, Manshouri T, Jabbour E, et al. Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. Blood: J Am Soc Hematol. 2017;130:1125–31. doi: 10.1182/blood-2017-05-783225. - DOI - PMC - PubMed

Publication types

MeSH terms