Evidence map›Paper›PMID 28228106›Full record

Trial reportJournal of hematology & oncology2017

Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial.

Srdan Verstovsek, Ruben A Mesa, Jason Gotlib, Vikas Gupta, John F DiPersio, John V Catalano, Michael W N Deininger, Carole B Miller, Richard T Silver, Moshe Talpaz and 12 more

Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of hematology & oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00952289 (A Randomized, Double-blind, Placebo-controlled Study of the JAK Inhibitor INCB018424 Tablets Administered Orally to Subjects With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis), which is not on this map. Cited by 243 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
243citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00952289 phase3completednot on this map

A Randomized, Double-blind, Placebo-controlled Study of the JAK Inhibitor INCB018424 Tablets Administered Orally to Subjects With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis

TypeinterventionalSponsorIncyte CorporationRan2009 to 2015Enrolled309ConditionsMPN (Myeloproliferative Neoplasms)ArmsRuxolitinib, Placebo
3 · Its place in the literature

Who cites it

243 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
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  4. Pooled it
  5. Selinexor Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Myelofibrosis: Phase III SENTRY Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
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  14. Randomized Trial of Ruxolitinib in Antiretroviral-Treated Adults With Human Immunodeficiency Virus.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Trial
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  17. Article
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183 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Srdan VerstovsekDivision of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 418, Houston, TX, 77030, USA. sverstov@mdanderson.org.
Ruben A MesaMayo Clinic Cancer Center, 13400 E. Shea Blvd, Scottsdale, AZ, 85259, USA.
Jason GotlibStanford Cancer Institute, 875 Blake Wilbur Drive, Room 2324, Stanford, CA, 94305, USA.
Vikas GuptaPrincess Margaret Cancer Center, University of Toronto, 610 University Avenue, Suite 5-217, Toronto, M5G 2M9, Canada.
John F DiPersioWashington University School of Medicine, 660S Euclid Ave., St. Louis, MO, 63110, USA.
John V CatalanoFrankston Hospital and Department of Clinical Haematology, Monash University, 2 Hastings Rd, Frankston, VIC, 3199, Australia.
Michael W N DeiningerUniversity of Utah Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
Carole B MillerSaint Agnes Cancer Institute, 900S Caton Ave., Baltimore, MD, 21229, USA.
Richard T SilverWeill Cornell Medical Center, 525 East 68th St., Payson Pavilion 3, New York, NY, 10021, USA.
Moshe TalpazUniversity of Michigan, 1500 E Medical Center Dr., Ann Arbor, MI, 48109, USA.
Elliott F WintonEmory University School of Medicine, 1365 C Clifton Rd. Suite 1152, Atlanta, GA, 30322, USA.
Jimmie H HarveyBirmingham Hematology and Oncology, 1024 First St North, Birmingham, AL, 35204, USA.
Murat O ArcasoyDuke University Health System, DUMC 3912, Durham, NC, 27710, USA.
Elizabeth O HexnerAbramson Cancer Center at the University of Pennsylvania, 3400 Civic Center Blvd., PCAM 2 West Pavilion, Philadelphia, PA, 19104, USA.
Roger M LyonsTexas Oncology and US Oncology Research, 4411 Medical Dr., San Antonio, TX, 78229, USA.
Ronald PaquetteCedars-Sinai, 10833 Le Conte Ave., 42-121 CHS, Los Angeles, CA, 90024, USA.
Azra RazaColumbia University Medical Center, Milstein Hospital Building, 6N-435, 177 Fort Washington Ave., New York, NY, 10032, USA.
Mark JonesIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA.
Deanna KornackiIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA.
Kang SunIncyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA.
Hagop KantarjianDivision of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 418, Houston, TX, 77030, USA.
COMFORT-I investigators

Funding

Mechanisms of resistance to ponatinib therapy in chronic myeloid leukemiaR01CA178397 · NCI · UNIVERSITY OF UTAH · PI DEININGER, MICHAEL W., O'HARE, THOMAS J. · 2014 to 2018
$2.6M
NCI NIH HHS R01 CA178397
6 · The paper itself

Abstract

backgroundThe randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial evaluated the JAK1/JAK2 inhibitor ruxolitinib in patients with intermediate-2/high-risk myelofibrosis. The primary and planned 3-year analyses of COMFORT-I data demonstrated that ruxolitinib-the first myelofibrosis-approved therapy-reduced splenomegaly and prolonged overall survival versus placebo. Here, we present the final 5-year results.

methodsPatients managed in Australia, Canada, and the USA were randomized centrally (interactive voice response system) 1:1 to oral ruxolitinib twice daily (15 or 20 mg per baseline platelet counts) or placebo. Investigators and patients were blinded to treatment. The secondary endpoints evaluated in this analysis were durability of a ≥35% reduction from baseline in spleen volume (spleen response) and overall survival, evaluated in the intent-to-treat population. Safety was evaluated in patients who received study treatment.

resultsPatients were randomized (September 2009-April 2010) to ruxolitinib (n = 155) or placebo (n = 154). At termination, 27.7% of ruxolitinib-randomized patients and 25.2% (28/111) who crossed over from placebo were on treatment; no patients remained on placebo. Patients randomized to ruxolitinib had a median spleen response duration of 168.3 weeks and prolonged median overall survival versus placebo (ruxolitinib group, not reached; placebo group, 200 weeks; HR, 0.69; 95% CI, 0.50-0.96; P = 0.025) despite the crossover to ruxolitinib. The ruxolitinib safety profile remained consistent with previous analyses. The most common new-onset all-grade nonhematologic adverse events starting <12 versus ≥48 months after ruxolitinib initiation were fatigue (29.0 vs 33.3%) and diarrhea (27.8 vs 14.6%). New-onset grade 3 or 4 anemia and thrombocytopenia both primarily occurred within the first 6 months, with no cases after 42 months. The most common treatment-emergent adverse event-related deaths in the ruxolitinib-randomized group were sepsis (2.6%), disease progression (1.9%), and pneumonia (1.9%).

conclusionThe final COMFORT-I results continue to support ruxolitinib as an effective treatment for patients with intermediate-2/high-risk MF.

trial registrationClinicalTrials.gov, NCT00952289.

Indexed as

DiarrheaDisease ProgressionDouble-Blind MethodFatigueFollow-Up StudiesHumansJanus KinasesNitrilesPneumoniaPrimary MyelofibrosisPyrazolesPyrimidinesRisk AssessmentSepsisSplenomegalySurvival RateJanus KinasesNitrilesPyrazolesPyrimidinesruxolitinibJAKJanus kinaseMyelofibrosis

Identifiers

PMID28228106
PMCPMC5322633

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.