What are the risks of not treating anemia in a high‑risk, JAK2‑positive primary myelofibrosis patient already receiving ruxolitinib (Jakafi)?

Risk of Not Treating Anemia in High-Risk, JAK2-Positive Primary Myelofibrosis Patients on Ruxolitinib

Untreated anemia in high-risk myelofibrosis patients already receiving ruxolitinib should not delay or prevent continuation of JAK inhibitor therapy, as withholding treatment risks disease progression, worsening splenomegaly, and reduced survival, while anemia itself can be managed without discontinuing ruxolitinib. 1, 2

Primary Risks of Untreated Anemia in This Population

Disease Progression and Mortality

• High-risk myelofibrosis patients have inherently short survival, and the modest survival gains achieved with ruxolitinib are critical even when anemia is present 1
• Ruxolitinib improves overall survival in intermediate-2 or high-risk myelofibrosis compared to best available therapy, and this benefit should not be sacrificed due to anemia concerns 3, 4
• The survival benefit of ruxolitinib persists regardless of baseline anemia status or development of treatment-emergent anemia 5

Symptom Burden and Quality of Life

• Untreated myelofibrosis leads to progressive splenomegaly, constitutional symptoms (fatigue, night sweats, weight loss), and cachexia that significantly impair quality of life 1, 6
• Ruxolitinib provides rapid and durable reduction in splenomegaly (51% response rate) and constitutional symptoms (42% response rate) independent of anemia status 4
• Patients receiving ruxolitinib demonstrate improvements in overall quality-of-life measures and reduction in myelofibrosis-associated symptoms, even when anemia develops 6

Spleen-Related Complications

• Without JAK inhibitor therapy, spleen size increases progressively (4% increase in palpable spleen length in untreated patients vs. 56% decrease with ruxolitinib at 48 weeks) 6
• Massive splenomegaly causes early satiety, abdominal discomfort, and contributes to cachexia 1

Evidence Supporting Treatment Despite Anemia

Clinical Trial Data

• In the REALISE study of anemic MF patients (hemoglobin <10 g/dL), 70% achieved ≥50% reduction in palpable spleen length with a reduced-dose ruxolitinib strategy 2
• Median hemoglobin levels remained stable and transfusion requirements did not increase compared with baseline in anemic patients receiving ruxolitinib 2
• The JUMP trial post-hoc analysis showed no differences in spleen response or overall survival between patients with versus without new-onset or worsening anemia during ruxolitinib treatment 5

Real-World Evidence

• In real-world practice, 88.3% of patients with baseline anemia maintained ruxolitinib doses ≥10 mg twice daily, with only 1.1% discontinuing for anemia 7
• Among patients with anemia at diagnosis, 79.7% had improved symptoms and 62.7% had improved spleen size with ruxolitinib treatment 7
• Most patients tolerated ruxolitinib for nearly 2 years despite baseline anemia or thrombocytopenia 7

Management Strategy for Anemia While Continuing Ruxolitinib

Combination Approaches

• Anemia in myelofibrosis can be managed with concurrent therapies while maintaining ruxolitinib 1
• Available options include danazol, erythropoiesis-stimulating agents (ESAs), immunomodulatory drugs (thalidomide, lenalidomide, pomalidomide), and steroids 1
• Anemia response rates to immunomodulatory drugs range from 20-30%, while ESAs and androgens achieve 20-60% response rates 1

Dosing Adjustments

• A reduced starting dose strategy (10 mg twice daily for 12 weeks) with delayed up-titration based on efficacy and platelet counts is effective in anemic patients 2
• Dose interruptions or reductions can manage hematologic toxicities without requiring permanent discontinuation 6

Critical Pitfalls to Avoid

Do Not Withhold Ruxolitinib Due to Anemia

• It is unnecessary to delay or withhold ruxolitinib because of co-existent or treatment-emergent anemia 2
• The presence of anemia should not prevent initiation or continuation of JAK inhibitor therapy in high-risk patients 5, 7

Recognize Anemia as Manageable

• Anemia is both a hallmark of myelofibrosis and an on-target effect of ruxolitinib due to JAK-STAT signaling's critical role in erythropoiesis 1
• Most anemia-related adverse events can be managed with dose adjustments or transfusions without discontinuing therapy 6

Monitor for Disease Progression

• Without treatment, high-risk myelofibrosis progresses to accelerated phase (10-19% blasts) or blast phase/AML (≥20% blasts), which have extremely poor outcomes 1
• No current therapy reliably prevents progression of myelofibrosis to acute myeloid leukemia, making disease control with ruxolitinib essential 1