Alleviating anemia and thrombocytopenia in myelofibrosis patients

Abstract

Anemia and thrombocytopenia are frequent clinical manifestations of myelofibrosis as well as important prognostic factors of the disease. Concerning the treatment of anemia, the first step should be the correction of reversible contributing factors, such as possible iron, folate and vitamin B12 deficiency. Then, treatment options include erythropoiesis stimulating agents, androgens, immunomodulating drugs, corticosteroids, and splenectomy. Anemia responses may also be observed in some patients treated with JAK inhibitors. However, most patients eventually fail to such therapies and become transfusion dependent. Some of the aforementioned therapies can also improve thrombocytopenia, but the responses are usually observed in patients with moderate platelet count decrease. Allogeneic hematopoietic stem cell transplantation, the only curative treatment of myelofibrosis, can be an alternative for selected patients with cytopenias who are refractory to conventional therapies. However, for the majority of patients, the management of anemia and severe thrombocytopenia remains an unmet need.

Inflammatory functional iron deficiency common in myelofibrosis, contributes to anaemia and impairs quality of life. From the Nordic MPN study Group

“…MF has the most severe symptom burden of the MPNs, and anaemia is an important reason for the fatigue, which is the most common and pronounced symptom of MF patients . The anaemia can be treated with erythropoiesis‐stimulating agents, cortisone, androgens or thalidomide plus cortisone, but the response rate varies and anaemia treatment is still an unmet need in this disease …”

Predictive factors for anemia response to erythropoiesis‐stimulating agents in myelofibrosis

“…Moreover, anemia is the feature most consistently associated with a poor prognosis in PMF . Its pathogenesis is multifactorial, including decreased bone marrow production, shortened red blood cells (RBC) survival, hypersplenism, and, occasionally, iron, folate or vitamin B12 deficiency . Besides, the anemia can be exacerbated as a consequence of the cytoreductive drugs, such as hydroxycarbamide or the JAK inhibitors, instituted to control the myeloproliferative manifestations of MF.…”

MOMENTUM: Momelotinib Vs Danazol in Patients with Myelofibrosis Previously Treated with JAKi Who Are Symptomatic and Anemic

“…Existing approaches for the management of MF-associated anemia include transfusion, erythropoiesis-stimulating agents in patients with low serum erythropoietin levels, corticosteroids, androgens (including danazol [DAN]), immunomodulatory imide drugs and splenectomy. The clinical activity of these has been modest and often limited to patient subsets, and none improve survival [3,[19][20][21]. This minimal effectiveness may be attributed to their inability to directly address the underlying causes of MF-associated anemia, including chronic inflammation and iron restriction within erythroid progenitors [22][23][24][25].…”