Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multicentre study
Claire N. Harrison,Nicolaas Schaap,Alessandro M. Vannucchi,Jean-Jacques Kiladjian,Ramon V. Tiu,Pierre Zachee,Eric Jourdan,Elliott F. Winton,Richard T. Silver,Harry C. Schouten,Francesco Passamonti,Sonja Zweegman,Moshe Talpaz,Joanne Lager,Zhenming Shun,Ruben A. Mesa +15 more
TLDR
A phase 2 study investigating the efficacy and safety of fedratinib, a JAK2-selective inhibitor, in patients with ruxolitinib-resistant or rUXolitinIB-intolerant myelofibrosis met its primary endpoint, suggesting that patients withRuxolit inib- resistant or ruxolidinib -intolerants myel ofibrosis might achieve significant clinical benefit with fedrat inib, albeit at the cost of some potential toxicityAbout:
This article is published in The Lancet Haematology.The article was published on 2017-07-01 and is currently open access. It has received 226 citations till now. The article focuses on the topics: Ruxolitinib & Pacritinib.read more
Citations
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The JAK/STAT signaling pathway: from bench to clinic.
TL;DR: In this article, the authors discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway and highlight the role of the pathway and its inhibitors in various diseases.
Journal ArticleDOI
Lipid Accumulation and Chronic Kidney Disease
Zhibo Gai,Tianqi Wang,Michele Visentin,Gerd A. Kullak-Ublick,Gerd A. Kullak-Ublick,Xianjun Fu,Zhenguo Wang +6 more
TL;DR: Lifestyle interventions, especially dietary adjustments, and lipid-lowering drugs can contribute to improve the clinical outcome of patients with CKD.
Journal ArticleDOI
JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders.
William Vainchenker,Emilie Leroy,Emilie Leroy,Laure Gilles,Caroline Marty,Caroline Marty,Isabelle Plo,Isabelle Plo,Stefan N. Constantinescu,Stefan N. Constantinescu +9 more
TL;DR: The strong anti-inflammatory effects of the JAK inhibitors appear as a very promising therapeutic approach for many inflammatory and auto-immune diseases.
Journal ArticleDOI
Roles of JAK2 in Aging, Inflammation, Hematopoiesis and Malignant Transformation
TL;DR: The current knowledge on JAK2 in clonal hematopoiesis during aging, the role of JAK-signaling in inflammation and lymphocyte biology and JAK1 function in age-related diseases and malignant transformation are summarized.
Journal ArticleDOI
Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs.
Massimo Gadina,Catrina A. Johnson,Daniella M. Schwartz,Michael Bonelli,Sarfaraz Hasni,Yuka Kanno,Paul S. Changelian,Arian Laurence,John J. O'Shea +8 more
TL;DR: Clinical data pertaining to the first generation of JAK inhibitors and their clinical indications are reviewed, additional opportunities for targeting this pathway are discussed, and some of the challenges that lie ahead are laid out.
References
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The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes
James W. Vardiman,Juergen Thiele,Daniel A. Arber,Richard D. Brunning,Michael J. Borowitz,Anna Porwit,Nancy L. Harris,Michelle M. Le Beau,Eva Hellström-Lindberg,Ayalew Tefferi,Clara D. Bloomfield +10 more
TL;DR: The classification of myeloid neoplasms and acute leukemia is highlighted with the aim of familiarizing hematologists, clinical scientists, and hematopathologists not only with the major changes in the classification but also with the rationale for those changes.
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A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis
Srdan Verstovsek,Ruben A. Mesa,Jason Gotlib,Richard S. Levy,Vikas Gupta,John F. DiPersio,John Catalano,Michael W. Deininger,Michael W. Deininger,Carole B. Miller,Richard T. Silver,Moshe Talpaz,Elliott F. Winton,Jimmie H. Harvey,Murat O. Arcasoy,Elizabeth O. Hexner,Roger M. Lyons,Ronald Paquette,Azra Raza,Kris Vaddi,Susan Erickson-Viitanen,Iphigenia L. Koumenis,William Sun,Victor Sandor,Hagop M. Kantarjian +24 more
TL;DR: Ruxolitinib provided significant clinical benefits in patients with myel ofibrosis by reducing spleen size, ameliorating debilitating myelofibrosis-related symptoms, and improving overall survival.
Journal ArticleDOI
Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2
Jyoti Nangalia,Charles E. Massie,E J Baxter,Francesca L. Nice,Gunes Gundem,David C. Wedge,Edward Avezov,Juan Li,Karoline Kollmann,David G. Kent,Athar Aziz,Anna L. Godfrey,Jonathon Hinton,Inigo Martincorena,P Van Loo,Amy V. Jones,Paola Guglielmelli,P. S. Tarpey,Heather P. Harding,J.D. Fitzpatrick,C.T. Goudie,Christina A. Ortmann,Stephen J. Loughran,Keiran Raine,David R. Jones,Adam Butler,Jon W. Teague,Sarah O’Meara,Stuart McLaren,M. Bianchi,Yvonne Silber,D. Dimitropoulou,David Bloxham,L. Mudie,Mark Maddison,Bruce W. S. Robinson,Clodagh Keohane,Cathy MacLean,Kate Hill,Kim Orchard,Sudhir Tauro,Ming-Qing Du,Mel Greaves,David G. Bowen,Brian J. P. Huntly,Claire N. Harrison,Nicholas C.P. Cross,David Ron,Alessandro M. Vannucchi,Elli Papaemmanuil,Peter J. Campbell,Anthony R. Green +51 more
TL;DR: Somatic mutations in the endoplasmic reticulum chaperone CALR were found in a majority of patients with myeloproliferative neoplasms with nonmutated JAK2, a finding consistent with its role as an initiating mutation in some patients.
Journal ArticleDOI
JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis.
Claire N. Harrison,Jean-Jacques Kiladjian,Haifa Kathrin Al-Ali,Heinz Gisslinger,Roger J. Waltzman,Viktoriya Stalbovskaya,Mari McQuitty,Deborah S. Hunter,Richard S. Levy,Laurent Knoops,Francisco Cervantes,Alessandro M. Vannucchi,Tiziano Barbui,Giovanni Barosi +13 more
TL;DR: Continuous ruxolitinib therapy, as compared with the best available therapy, was associated with marked and durable reductions in splenomegaly and disease-related symptoms, improvements in role functioning and quality of life, and modest toxic effects.
Journal ArticleDOI
Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis
Claire N. Harrison,Alessandro M. Vannucchi,Jean-Jacques Kiladjian,Haifa Kathrin Al-Ali,Heinz Gisslinger,Laurent Knoops,Francisco Cervantes,Mark M. Jones,Kang Sun,Mari McQuitty,Viktoriya Stalbovskaya,Prashanth Gopalakrishna,T Barbui +12 more
TL;DR: It was shown that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits and there was no unexpected increased incidence of adverse events with longer exposure.
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