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J Hematol Oncol. 2017 Sep 29;10(1):156. doi: 10.1186/s13045-017-0527-7.

Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses.

Author information

1
The University of Texas MD Anderson Cancer Center, Division of Cancer Medicine, 1515 Holcombe Blvd, Unit 418, Houston, TX, 77030, USA. sverstov@mdanderson.org.
2
Stanford Cancer Institute, Stanford, CA, USA.
3
UT Health San Antonio Cancer Center - An NCI Designated Cancer Center, San Antonio, TX, USA.
4
Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, and Laboratorio Congiunto, University of Florence, Florence, Italy.
5
Centre d'Investigations Cliniques (INSERM CIC 1427), Hôpital Saint-Louis and Université Paris Diderot, Paris, France.
6
Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
7
Guy's and St. Thomas' NHS Foundation Trust, London, UK.
8
Cedars-Sinai Medical Center, Los Angeles, CA, USA.
9
Incyte Corporation, Wilmington, DE, USA.
10
Novartis Pharmaceutical Corporation, East Hanover, NJ, USA.
11
Novartis Pharma AG, Basel, Switzerland.
12
Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.

Abstract

BACKGROUND:

Myelofibrosis (MF) is associated with a variety of burdensome symptoms and reduced survival compared with age-/sex-matched controls. This analysis evaluated the long-term survival benefit with ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, in patients with intermediate-2 (int-2) or high-risk MF.

METHODS:

This was an exploratory analysis of 5-year data pooled from the phase 3 COMFORT-I and -II trials. In both trials, patients could cross over to ruxolitinib from the control group (COMFORT-I, placebo; COMFORT-II, best available therapy). All continuing patients in the control groups crossed over to ruxolitinib by the 3-year follow-up. Overall survival (OS; a secondary endpoint in both trials) was evaluated using pooled intent-to-treat data from patients randomized to ruxolitinib or the control groups. OS was also evaluated in subgroups stratified by baseline anemia and transfusion status at week 24.

RESULTS:

A total of 528 patients were included in this analysis; 301 were originally randomized to ruxolitinib (COMFORT-I, n = 155; COMFORT-II, n = 146) and 227 to control (n = 154 and n = 73, respectively). The risk of death was reduced by 30% among patients randomized to ruxolitinib compared with patients in the control group (median OS, 5.3 vs 3.8 years, respectively; hazard ratio [HR], 0.70 [95% CI, 0.54-0.91]; P = 0.0065). After correcting for crossover using a rank-preserving structural failure time (RPSFT) method, the OS advantage was more pronounced for patients who were originally randomized to ruxolitinib compared with patients who crossed over from control to ruxolitinib (median OS, 5.3 vs 2.3 years; HR [ruxolitinib vs RPSFT], 0.35 [95% CI, 0.23-0.59]). An analysis of OS censoring patients at the time of crossover also demonstrated that ruxolitinib prolonged OS compared with control (median OS, 5.3 vs 2.4 years; HR [ruxolitinib vs censored at crossover], 0.53 [95% CI, 0.36-0.78]; P = 0.0013). The survival benefit with ruxolitinib was observed irrespective of baseline anemia status or transfusion requirements at week 24.

CONCLUSIONS:

These findings support ruxolitinib treatment for patients with int-2 or high-risk MF, regardless of anemia or transfusion status. Further analyses will be important for exploring ruxolitinib earlier in the disease course to assess the effect on the natural history of MF.

TRIAL REGISTRATION:

ClinicalTrials.gov identifiers, NCT00952289 and NCT00934544 .

KEYWORDS:

Anemia; Myelofibrosis; Overall survival; Ruxolitinib; Transfusion

PMID:
28962635
PMCID:
PMC5622445
DOI:
10.1186/s13045-017-0527-7
[Indexed for MEDLINE]
Free PMC Article

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