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Cited by 260Myeloproliferative Neoplasms: Diagnosis and TreatmentChronic Lymphocytic Leukemia ResearchAcute Myeloid Leukemia Research

A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis

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Vannucchi, A. M., Kantarjian, H. M., Kiladjian, J.-J., Gotlib, J., Cervantes, F., Mesa, R. A., Sarlis, N. J., Peng, W. +8 more·2015·Haematologica
DOI 10.3324/haematol.2014.119545PMC PMC4800694
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Abstract

Ruxolitinib, a potent Janus kinase 1/2 inhibitor, resulted in rapid and durable improvements in splenomegaly and disease-related symptoms in the 2 phase III COMFORT studies. In addition, ruxolitinib was associated with prolonged survival compared with placebo (COMFORT-I) and best available therapy (COMFORT-II). We present a pooled analysis of overall survival in the COMFORT studies using an intent-to-treat analysis and an analysis correcting for crossover in the control arms. Overall, 301 patients received ruxolitinib (COMFORT-I, n=155; COMFORT-II, n=146) and 227 patients received placebo (n=154) or best available therapy (n=73). After a median three years of follow up, intent-to-treat analysis showed that patients who received ruxolitinib had prolonged survival compared with patients who received placebo or best available therapy [hazard ratio=0.65; 95% confidence interval (95%CI): 0.46-0.90; P=0.01]; the crossover-corrected hazard ratio was 0.29 (95%CI: 0.13-0.63). Both patients with intermediate-2- or high-risk disease showed prolonged survival, and patients with high-risk disease in the ruxolitinib group had survival similar to that of patients with intermediate-2-risk disease in the control group. The Kaplan-Meier estimate of overall survival at week 144 was 78% in the ruxolitinib arm, 61% in the intent-to-treat control arm, and 31% in the crossover-adjusted control arm. While larger spleen size at baseline was prognostic for shortened survival, reductions in spleen size with ruxolitinib treatment correlated with longer survival. These findings are consistent with previous reports and support that ruxolitinib offers a survival benefit for patients with myelofibrosis compared with conventional therapies. (clinicaltrials.gov identifiers: COMFORT-I, NCT00952289; COMFORT-II, NCT00934544).

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  • Ruxolitinib has promising activity in PMF patients, showing reduction in splenomegaly, improvement in disease-related symptoms, and increased overall survival compared with placebo or best available therapy.

    “Ruxolitinib, a JAK1/JAK2 inhibitor, has demonstrated promising activity in PMF patients, showing increased benefit across several end points, e.g., reduction in splenomegaly, improvement in disease-related symptoms, and increased overall survival, when compared with placebo or best available therapy”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Vannucchi et al., 2015

    The Abstract (p. 1) reports reduced splenomegaly, improved disease-related symptoms, and prolonged survival with ruxolitinib compared with placebo or best available therapy. The Methods (p. 2) show that the trials included patients with primary myelofibrosis, but also patients with secondary myelofibrosis; the cited results are not reported specifically for the PMF subgroup. (LLM, conf=0.82)

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References 36 · Cited by 260

Research works printed but not linked: 23

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Authors
Vannucchi, A. M., Kantarjian, H. M., Kiladjian, J.-J., Gotlib, J., Cervantes, F., Mesa, R. A., Sarlis, N. J., Peng, W., Sandor, V., Gopalakrishna, P., Hmissi, A., Stalbovskaya, V., Gupta, V., Harrison, C., Verstovsek, S., & on behalf of the COMFORT Investigators
Affiliations
  • University of Florence (IT)
  • The University of Texas MD Anderson Cancer Center (US)
  • Université Paris Cité (FR)
  • Stanford Cancer Institute (US)
  • Hospital Clínic de Barcelona (ES)
  • Mayo Clinic (US)
  • Incyte (United States) (US)
  • Novartis (Switzerland) (CH)
  • University of Toronto (CA)
  • Guy's Hospital (GB)
ORCID
Venue
Haematologica
Publisher
Ferrata Storti Foundation (Haematologica)
Published
2015-06-11
Volume
100
Issue
9
Pages
1139-1145
ISSN
  • 0390-6078 (ISSN-L)
  • 1592-8721
DOI
10.3324/haematol.2014.119545
PMC
PMC4800694
OpenAlex
W2126532431
Cited by
260
References
36
Citations by year
2026: 20 · 2025: 11 · 2024: 26 · 2023: 26 · 2022: 24 · 2021: 12 · 2020: 19 · 2019: 15 · 2018: 21 · 2017: 31 · 2016: 41 · 2015: 11 · 2014: 3
FWCI
19.41
Type
journal article
Language
en
Open access
Locations
  • Haematologica (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion)
  • Florence Research (University of Florence) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • IrInSubria (University of Insubria) (submittedVersion)
Funders
  • University of Texas MD Anderson Cancer Center ((CA016672))
  • National Cancer Institute (CA 016672, P30CA016672)
Topics
  • Health Sciences › Medicine › Genetics › Myeloproliferative Neoplasms: Diagnosis and Treatment
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords
ruxolitinib, myelofibrosis, overall survival, JAK inhibitors, splenomegaly, spleen size reduction, disease risk stratification, prognostic factors
MeSH terms
Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Male, Middle Aged, Nitriles, Pyrazoles, Pyrimidines, Risk Factors, Survival Rate, Disease-Free Survival, Janus Kinase 1, Janus Kinase 2, Primary Myelofibrosis

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