Patients with myelofibrosis who develop anemia while receiving ruxolitinib (Jakafi) treatment continue to derive clinical benefit from the therapy, according to new findings from a post-hoc analysis of the phase 3b JUMP trial presented at the 2024 European Hematology Association Congress.
The analysis of 2,233 patients from the largest ruxolitinib trial in myelofibrosis to date found that overall survival remained comparable between patients who developed new or worsening anemia and those who did not. Among baseline anemic patients, the median overall survival was 58.3 months (95% CI, 52.6-not evaluable) in those with new or worsening anemia (n = 361) compared with not evaluable (95% CI, 52.7-NE) in those without new or worsening anemia (n = 486; HR, 1.08; 95% CI, 0.77-1.51; P = .66).
"Dose-dependent anemia is one of the adverse effects of ruxolitinib therapy," explained Haifa Kathrin Al-Ali, MD, lead study author and professor of hematology at the University Hospital Halle (Saale) in Germany. "A previous analysis of 2 phase 3 trials showed that new or worsening anemia did not diminish the clinical benefit of ruxolitinib therapy."
Validating Previous Findings in Real-World Setting
The JUMP trial served as a global, single-arm expanded-access study evaluating ruxolitinib treatment in patients with myelofibrosis in a setting comparable to routine clinical practice. The current analysis aimed to validate findings from the earlier COMFORT-I and COMFORT-II trials using data from this larger, more diverse patient population.
Eligible patients were at least 18 years old with primary or secondary myelofibrosis classified as high, intermediate-2, or intermediate-1 risk according to International Prognostic Scoring System criteria. Patients with intermediate-1 risk disease required palpable splenomegaly of at least 5 cm from the costal margin.
All patients received ruxolitinib twice daily with dosing based on platelet counts: 5 mg for platelet counts of 50 x 10⁹/L to less than 100 x 10⁹/L; 15 mg for counts of 100 x 10⁹/L to 200 x 10⁹/L; or 20 mg for counts over 200 x 10⁹/L. The analysis stratified patients by baseline anemia and transfusion status, defining nonanemic as hemoglobin levels over 100 g/L.
Sustained Efficacy Across Patient Subgroups
Baseline characteristics were well balanced between the new/worsening anemia (n = 1,117) and no new/worsening anemia (n = 1,116) groups. The median age was 68.0 years versus 66.0 years, respectively, with median time since initial diagnosis of 24.9 months versus 26.9 months. Most patients in both groups had palpable spleen (93.8% vs 93.1%) and median platelet counts of at least 200 x 10⁹/L (65.0% vs 60.2%).
Spleen response rates demonstrated the maintained efficacy of ruxolitinib despite anemia development. At week 24, baseline nonanemic patients in the new/worsening anemia group achieved spleen length reduction of at least 50% at a rate of 31.5% compared with 31.2% in those without new or worsening anemia (P = .93). By week 48, these rates were 35.6% versus 26.1%, respectively (P = .02).
Symptom response, measured by FACT-Lym total score improvements, also remained consistent. At week 24, baseline nonanemic patients achieved a minimum 6.5-point increase at rates of 34.5% versus 34.0% (P = .86) in the new/worsening anemia and no new/worsening anemia groups, respectively.
Clinical Implications for Treatment Decisions
The median dose exposure was comparable between groups at 12.2 months (range, 0.2-59.7) for patients with new or worsening anemia and 12.5 months (range, 0-58.1) for those without. This suggests that anemia development did not lead to significant treatment discontinuation or dose reductions that would compromise efficacy.
"These results from JUMP based on a broad patient population in a real-world setting, including those with platelet counts of less than 100 x 10⁹/L and lower-risk patients with myelofibrosis, support the use of ruxolitinib in patients with myelofibrosis regardless of baseline anemia or the development of treatment-related anemia," Al-Ali concluded.
The findings provide reassurance for clinicians managing myelofibrosis patients who develop anemia during ruxolitinib treatment, supporting continued therapy rather than discontinuation based solely on hematologic adverse effects. The results validate previous observations from the COMFORT trials in a larger, more representative patient population that includes those typically excluded from randomized controlled trials.
