Myelofibrosis-Related Anemia: Current and Emerging Therapeutic Strategies

Abstract

Abstract. Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder characterized by pathological myeloproliferation and aberrant cytokine production resulting in progressive fibrosis, inflammation, and functional compromise of the bone marrow niche. Patients with MF develop splenomegaly (due to extramedullary hematopoiesis), hypercatabolic symptoms (due to overexpression of inflammatory cytokines), and anemia (due to bone marrow failure and splenic sequestration). MF remains curable only with allogeneic hematopoietic stem cell transplantation (ASCT), a therapy that few MF patients are deemed fit to undergo. The goals of treatment are thus often palliative. The approval of the JAK inhibitor ruxolitinib has done much to address the burden of splenomegaly and constitutional symptoms of patients with MF; however, therapy-related anemia is often an anticipated downside. Anemia thus remains a challenge in the management of MF and represents a major unmet need. Intractable anemia depresses quality of life, portends poor outcomes, and can act to restrict access to palliative JAK inhibition in some patients. While therapies for MF-related anemia do exist, they are limited in their efficacy, durability, and tolerability. Therapies currently in development promise improved anemia-specific outcomes; however, are still early in the pathway to regulatory approval and regular clinical use. In this review, we will discuss established and emerging treatments for MF-related anemia. We will give particular attention to developmental therapies which herald significant progress in the understanding and management of MF-related anemia.