Ruxolitinib Improves Outcomes in Myelofibrosis Regardless of Anemia, Transfusion Status


Post-hoc analysis results showed a reduction in spleen volume of 35% with ruxolitinib in patients with myelofibrosis.

pacritinib molecular structure, 3d model molecule, macrocyclic protein kinase inhibitor, structural chemical formula view from a microscope | Image Credit: © Сергей Шиманович

Image Credit: © Сергей Шиманович

Findings from a post-hoc analysis of the phase 3 COMFORT-I (NCT00952289) and -II (NCT00934544) revealed that ruxolitinib (Jakafi) improves spleen volume and tumor symptom score (TSS) in patients with myelofibrosis, irrespective of their anemia and transfusion status, according to a presentation at the 2023 EHA Congress.1

Results showed that the reduction in spleen volume of 35% or greater from baseline (SVR35) rates at week 24 in patients with new or worsening anemia up to week 12 were 48.8%, 33.3%, and 41.4%, respectively, for those who were nonanemic, anemic/nontransfusion dependent, and anemic/transfusion dependent at baseline. These rates were 43.2%, 23.1%, and 28.2%, respectively, in patients who did not have new or worsening anemia at week 24.

SVR35 at week 48 was achieved in 42.1%, 44.1%, and 34.6% of patients who had new or worsening anemia and were nonanemic, anemic/nontransfusion dependent, and anemic/transfusion dependent at baseline compared with 42.4%, 22.2%, and 27.3% in those who did not have new or worsening anemia.

A 50% or greater reduction in TSS at week 24 was achieved by 51.1%, 42.1%, and 46.7% of those with new or worsening anemia up to week 12 and who were nonanemic, anemic/nontransfusion dependent, or anemic/transfusion dependent at baseline. In patients who did not have new or worsening anemia up to week 12, these rates were 42.9%, 40.0%, and 54.2%, respectively.

Ruxolitinib, a JAK1/2 inhibitor, is indicated for patients with intermediate- or high-risk myelofibrosis. The FDA approval for ruxolitinib in this setting was based off findings from the COMFORT-I2 and COMFORT-II3 trials. Findings showed that ruxolitinib demonstrated a reduction in spleen volume, improved myelofibrosis-related symptoms, and prolonged overall survival. This was in comparison with placebo in COMFORT-I and with best available therapy (BAT) in COMFORT-II.

Transient dose-dependent anemia is a treatment-related adverse effect (TRAE) that has been observed with ruxolitinib. In COMFORT-I, grade 3/4 anemia occurred in 45.2% of patients on ruxolitinib vs 19.2% with placebo. In COMFORT-II, the most frequently reported serious adverse effect in both arms was anemia (5% with ruxolitinib vs 4% with BAT).

Therefore, in the post-hoc analysis presented during the congress, investigators sought to determine how new or worsening anemia from ruxolitinib treatment impacts SVR and TSS in this patient population.

Patients were treated with ruxolitinib twice daily with an initial dose based on platelet count. For those with a platelet count of 100 to 200 x 109/L, the dose was 15 mg vs 20 mg for those whose platelet count was above 200 x 109/L. Stratification factors included anemia status at baseline (yes vs no) and transfusion status at baseline (transfusion dependent vs nontransfusion dependent).

Anemia was defined as hemoglobin less than 100 g/L and patients were considered transfusion dependent if they received 2 or more units of red blood cells over 8 to 12 weeks before their first dose of ruxolitinib. Investigators stratified outcomes via presence or absence of new or worsening anemia postbaseline, which was defined as a decrease in hemoglobin of at least 15 g/L or new transfusion requirement at weeks 4, 8, or 12.

Specifically, investigators assessed patients with a reduction in spleen volume of at least 35% from baseline from the pooled COMFORT-I/-II data at weeks 24 and 48, and with at least a 50% reduction in modified Myelofibrosis Symptom Assessment Form TSS at week 24, from the COMFORT-I data.

A total of 277 patients were included in the analysis. Regarding baseline characteristics, the median age ranged from 65.0 to 71.0 years, and between 47% and 56% were male. More than half of patients were baseline nonanemic (n = 154; 55.6%) 19.9% (n = 55) were anemic/nontransfusion dependent, and 24.5% (n = 68) were anemia/transfusion dependent.


1. Al-Ali HK, Mesa R, Hamer-Maansson JE, Braunstein E, Harrison, C. Effect of new or worsening anemia on clinical outcomes in patients with myelofibrosis (MF) treated with ruxolitinib (RUX): a post hoc analysis of the COMFORT-I and -II trials. Presented at: 2023 European Hematology Association Congress; June 8-11, 2023; Frankfurt, Germany. Abstract PB2185.

2. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799-807. doi:10.1056/NEJMoa1110557

3. Harrison C, Kiladjian J-J, Al-Ali HK, et al. JAK Inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med .2012;366:787-798. doi:10.1056/NEJMoa1110556.

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