How I treat myelofibrosis-related anemia

The MPN Hub spoke with Aaron Gerds, Cleveland Clinic Taussig Cancer Institute, Cleveland, US. We asked about the treatment of patients with myelofibrosis-associated anemia. 

During this interview, Gerds discussed the burden and management of myelofibrosis-associated anemia. He explained its prevalence, prognostic importance, and multifactorial causes. Gerds also reviewed currently available therapies, combination strategies, and the need for further disease-modifying approaches. 

Key learnings 

• Anemia is common in myelofibrosis, affecting approximately 40% of patients at the time of presentation and developing in nearly all patients over time.¹ 

• The severity of anemia is prognostic, with worse anemia linked to shorter survival and transfusion dependence associated with the poorest outcomes. 

• Myelofibrosis-associated anemia is linked to various causes, including ineffective erythropoiesis, inflammation with elevated hepcidin, drug effects, splenomegaly-related destruction, and sometimes autoimmune hemolysis. 

• Because multiple mechanisms drive anemia, no single therapy is universally effective, and a range of approaches is required. 

• Supportive agents such as erythropoiesis-stimulating agents, luspatercept, and danazol can improve anemia but do not alter the underlying disease biology of myelofibrosis. 

• These supportive therapies are most often used when anemia is the primary concern, especially in patients without significant splenomegaly or symptom burden, and can be given with or without Janus kinase (JAK) inhibitors, allowing for safe use in combination when splenomegaly and symptoms are controlled. 

• JAK inhibitors that also inhibit ACVR1, such as momelotinib and pacritinib, provide dual benefit by reducing splenomegaly and symptoms through JAK inhibition while improving anemia through ACVR1 inhibition and hepcidin reduction. 

• Pacritinib also targets Interleukin 1 receptor associated kinase 1 (IRAK1), supporting its role in cytopenic myelofibrosis where anemia is central. 

• Allogeneic stem cell transplantation is currently the only treatment that can completely reverse anemia by eradicating disease and restoring erythropoiesis. 

• Emerging therapies such as pelabresib show promise in improving anemia by addressing disease biology, pointing toward future disease-modifying strategies. 

• While supportive agents remain essential in current practice, the ultimate goal is to develop therapies that fundamentally modify the pathophysiology of myelofibrosis and restore normal blood cell production.