Ruxolitinib Improves OS in Patients With Myelofibrosis vs Hydroxyurea Alone

An update to the ERNEST study found a survival benefit in ruxolitinib for the treatment of myelofibrosis in both the first and second line vs hydroxyurea.

Patients with myelofibrosis (MF) face a lower overall survival (OS) rate than the general public, and the condition has been associated with significant effects on patient quality of life. An update to the European Registry for Myeloproliferative Neoplasms: Toward a Better Understanding of Epidemiology, Survival, and Treatment (ERNEST) study aimed to analyze the OS impact of the JAK1/2 inhibitor ruxolitinib using real-world data.

Historically, treatment options for MF, a rare type of bone marrow cancer that affects red blood cell production and has a median OS of 6 to 7 years, are limited in their symptom-relieving efficacy. Stem cell transplantation, which is only performed on a minority of patients with MF, is the sole curative approach thus far, according to the study authors.

Ruxolitinib works by reducing splenomegaly to improve constitutional symptoms and therefore quality of life. A post-hoc analysis of data from the COMFORT-I and COMFORT-II trials reported survival improvements with ruxolitinib, but given these studies were not powered to show OS effects, those findings are debatable, the authors noted. ERNEST prospectively enrolled patients with MF, aiming to assure the “reliability, representativeness, and comparability of real-world data across international centers with expertise in the management of MF.”

A total of 1292 patients at 13 centers in 5 European countries were enrolled in the ERNEST registry from February 2013 to May 2014. For this updated analysis, 282 of the original 1292 were excluded from the data pool. The current cohort comprised the remaining 1010 patients.

Of the overall cohort, 584 patients (57.8%) had primary MF, 207 (20.5%) had post–essential thrombocythemia MF, and 219 (21.7%) had post–polycythemia vera MF. Of the 1010 patients in the cohort, 365 died by the end of 2014 and the remaining 645 were updated through 2018. The median patient age was 63.7 years, and 59.9% were men.

At enrollment, 598 patients (59.2%) had received cytoreduction therapy for MF, 487 (48.2%) had only received hydroxyurea, and 108 (10.7%) received ruxolitinib. Of those who received ruxolitinib, 69 (64%) had received hydroxyurea and 2 (1.9%) had received interferon. Patients who received ruxolitinib were younger than those treated with only hydroxyurea (64.5 vs 67.0 years; P = .02) and had both massive splenomegaly (defined as > 20 cm r from the left costal margin) and constitutional symptoms compared with those given only hydroxyurea (36.6% vs 6.0% [P < .001] and 80% vs 49.1% [P = .03], respectively).

At a median follow-up of 5.2 years, 625 deaths had occurred, with a mortality rate of 10.9 per 100 person-years. Median OS was 6.2 years (95% CI, 2.8-12.6). In the overall population in the study, the median OS was not met in low-risk patients, was 7.7 years for intermediate-1 risk category patients, was 5 years for intermediate-2 patients, and was 2.8 years for high-risk patients. Risk categories were stratified according to International Prognostic Scoring System (IPSS) and Dynamic IPSS (DIPSS) risk groups.

Median OS of secondary MF (based on the MF secondary to polycythemia vera and essential thrombocythemia-prognostic model) was not reached for low-risk patients, was 6 years for patients with intermediate-1 risk, was 3.2 years for patients with intermediate-2 risk, and was 1.8 years for patients categorized as high risk.

The time to first treatment also differed between therapies. Median time to hydroxyurea treatment was 0 years, with a range of 0 to 1.2 years. Ruxolitinib had a median 4.5 years to first treatment, with a range of 2.2 to 6.7 years.

Patients who were treated with ruxolitinib had longer median OS compared with patients who received hydroxyurea alone, at 6.7 vs 5.1 years. “Notably, in the entire study population, the prognostic relevance of ruxolitinib exposure was mostly restricted to patients who, at the beginning of treatment, were in DIPSS higher risk categories,” the authors wrote.

Although age, high DIPPS category, and male sex negatively affected OS in this study, more recent diagnosis and ruxolitinib treatment were identified as protective variables.

A propensity score (PS) matching analysis was done to ensure comparability between patients who received hydroxyurea only vs those who received ruxolitinib as either first- or second-line treatment. There was no significant different in OS outcomes between ruxolitinib as first- or second-line treatment, and median OS was still higher in patients given ruxolitinib compared with those given hydroxyurea only (7.7 vs 3.4 years).

The study authors conclude that in recent years, ruxolitinib has been increasingly used to treat MF in European countries and is associated with a survival benefit.

“Compared with hydroxyurea, ruxolitinib treatment was associated with a significant benefit in terms of OS in multivariate analysis; benefit was also seen in PS analysis within the limits of small sample sizes,” the authors wrote. “Our study offers a unique opportunity to provide real-life evidence of the impact of ruxolitinib on survival in patients with primary or secondary MF.”

Reference

Guglielmelli P, Ghirardi A, Carobbio A, et al. Impact of ruxolitinib on survival of patients with myelofibrosis in the real world: update of the ERNEST Study. Blood Adv. 2022;6(2):373-375. doi:10.1182/bloodadvances.2021006006