Abstract
BackgroundMyelofibrosis (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.MethodsThis 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.ResultsA 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.ConclusionsThese 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 registrationClinicalTrials.gov identifiers, NCT00952289 and NCT00934544.
Highlights
Myelofibrosis (MF) is associated with a variety of burdensome symptoms and reduced survival compared with age-/sex-matched controls
30% among patients randomized to ruxolitinib compared with patients in the control group
After correcting for crossover using rank-preserving structural failure time (RPSFT), the overall survival (OS) advantage was more pronounced in patients who were originally randomized to ruxolitinib compared with patients who crossed over from control to ruxolitinib
Summary
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. Ruxolitinib is a Janus kinase (JAK)1/JAK2 inhibitor approved by the European Medicines Agency for the treatment of disease-related splenomegaly or symptoms in adult patients with primary MF (PMF), post–polycythemia vera MF (PPV-MF), and post–essential thrombocythemia MF (PET-MF) [6], and by the US Food and Drug Administration for intermediate or high-risk MF, including PMF, PPV-MF, and PET-MF [7]. Primary results from two long-term, pivotal phase 3 clinical trials (COMFORT-I and COMFORT-II) demonstrated that ruxolitinib reduced spleen volume, improved MF-related symptoms and quality-of-life measures, and was associated with prolonged OS in patients with intermediate-2 (int-2) or high-risk MF compared with controls [8–10]. Exploratory analyses of pooled 3-year data from the COMFORT trials showed that OS favored ruxolitinib regardless of baseline anemia status or development of new or worsening anemia post baseline [11]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have