Ruxolitinib Plus ESA or Danazol Maintains Efficacy in Patients With Myelofibrosis Who Have Anemia
Patients with myelofibrosis frequently present with anemia, and while ruxolitinib—the Janus kinase (JAK)1/JAK2 inhibitor—remains a cornerstone of therapy, it is known to induce dose-dependent anemia. New data from the large phase 3b JUMP trial suggest that supportive anemia management using erythropoiesis-stimulating agents (ESAs) or danazol does not compromise treatment efficacy and may enable maintenance of full-dose ruxolitinib in this challenging patient population.
The post-hoc analysis drew from JUMP, a single-arm, expanded-access study that enrolled 2233 adults with primary or secondary myelofibrosis and baseline platelet counts ≥ 50 × 10⁹/L. The analysis focused on 1343 patients with baseline anemia (hemoglobin < 12 g/dL) who were not receiving anemia therapy at enrollment. Of these, 101 patients (7.5%) initiated ESA or danazol within 3 months of trial entry and continued therapy for at least 3 months. A subset analysis was conducted for the 732 patients with hemoglobin < 10 g/dL, of whom 52 (7.1%) began anemia-directed treatment within the same timeframe.
Median time to initiation of ESA or danazol was 43 days from enrollment for the Hb<12 group, and 34 days for the more anemic Hb<10 subset. Nearly all patients (91%) had palpable splenomegaly at baseline. The addition of ESA or danazol produced outcomes consistent with the broader JUMP population, indicating no compromise in therapeutic benefit. By week 24, spleen length reduction was achieved in 36.6% of the Hb<12 cohort and 34.6% of the Hb<10 subset, compared with 31.5% in the overall JUMP population. Symptom response rates were likewise comparable—25.7% for Hb<12, 23.1% for Hb<10, and 26.9% for the total cohort.
Hemoglobin trends across both anemia groups were encouraging. Mean hemoglobin levels initially declined, reaching a nadir at week 4, but steadily recovered to exceed baseline values by week 48. This recovery trajectory paralleled continued exposure to ruxolitinib, with average doses remaining above 25 mg per day for the majority of study visits. The ability to maintain full-dose ruxolitinib was therefore not impaired by concurrent ESA or danazol use.
“For patients with anemia at myelofibrosis diagnosis who received ESA/danazol in combination with ruxolitinib, spleen and symptom responses were similar to those reported in the entire JUMP study population, and most patients tolerated ruxolitinib doses >25 mg daily,” the investigators reported.
The findings have direct implications for clinical practice and oncology care management. Ruxolitinib-associated anemia often prompts dose reductions that can blunt treatment efficacy; however, this analysis reinforces the value of supportive care interventions that preserve dose intensity. The data suggest that integrating anemia-directed therapy early in the course of ruxolitinib treatment can help sustain both hematologic stability and clinical response without sacrificing safety or efficacy.
For oncologists, these results provide reassurance that ESA or danazol can be used in tandem with ruxolitinib to manage anemia without compromising the drug’s primary disease-modifying benefits. For oncology payers and pathway decision-makers, the findings support continued inclusion of combined ruxolitinib and ESA/danazol strategies as part of comprehensive care pathways for myelofibrosis, particularly in patients with preexisting anemia.
Reference
Vachhani P, Repp J, Hamer-Maansson JE, Braunstein E, Bhatt V, Kathrin Al-Ali HK. MPN-993: clinical outcomes in patients with myelofibrosis treated with ruxolitinib and anemia-supporting medications. Clin Lymphoma Myeloma Leuk. 2025; 25(S683)(suppl 1). doi:10.1016/S2152-2650(25)02152-4
