From the Guidelines
Myelofibrosis is a rare bone marrow cancer that requires prompt management to improve symptoms and quality of life, with treatment options including medications like ruxolitinib, blood transfusions, and stem cell transplantation for eligible patients. Myelofibrosis belongs to a group of blood disorders called myeloproliferative neoplasms, where abnormal blood cells and fibers build up in the bone marrow, disrupting normal blood cell production 1. The condition can develop on its own (primary myelofibrosis) or as a progression from other blood disorders like polycythemia vera or essential thrombocythemia (secondary myelofibrosis) 1.
Key Symptoms and Treatment Options
- Fatigue, weakness, enlarged spleen, easy bruising or bleeding, bone pain, night sweats, and fever are common symptoms of myelofibrosis 1
- Treatment typically focuses on managing symptoms and may include:
- Medications like ruxolitinib (Jakafi) to reduce spleen size and improve symptoms
- Blood transfusions for anemia
- Stem cell transplantation for eligible patients, particularly those with intermediate-2 or high-risk disease 1
Risk Stratification and Management
- Risk stratification is crucial in determining the best course of treatment, with the Dynamic International Prognostic Scoring System (DIPSS)-Plus being the preferred method for risk stratification 1
- Allogeneic stem cell transplantation is recommended for transplant-eligible patients with high or intermediate-2 risk score, as well as those with intermediate-1 risk score who present with refractory, transfusion-dependent anemia, blasts in peripheral blood > 2%, adverse cytogenetics, or high-risk mutations 1
- Ruxolitinib is recommended as first-line approach for myelofibrosis-associated splenomegaly in patients with intermediate-2 or high-risk disease, and in highly symptomatic splenomegaly for those with intermediate-1 disease 1
From the Research
Definition and Characteristics of Myelofibrosis
- Myelofibrosis is a rare bone marrow disorder associated with a high symptom burden, poor prognosis, and shortened survival 2.
- It is characterized by stem cell-derived clonal proliferation that is often accompanied by somatic mutations, which are classified into driver mutations (JAK2, CALR, or MPL), subclonal mutations, and fibrosis on bone marrow biopsy 3.
- Myelofibrosis commonly demonstrates splenomegaly, constitutional symptoms, anemia, thrombocytosis, or thrombocytopenia, and patients may also be asymptomatic 3.
Treatment Options for Myelofibrosis
- Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for myelofibrosis 2, 3, 4.
- Ruxolitinib is an approved and reimbursed pharmacotherapy for non-HSCT candidates, particularly for transplant-ineligible myelofibrosis patients from intermediate-2- and high-risk groups and from the intermediate-1-risk group with splenomegaly 2.
- Other treatment options, including luspatercept, KER-050, momelotinib, pacritinib, pelabresib, PRM-151, imetelstat, and navitoclax, are being explored for the treatment of anemia in myelofibrosis 5.
Management of Myelofibrosis
- Ruxolitinib treatment should be continued as long as there is clinical benefit, and progressive dose tapering is recommended when stopping ruxolitinib 2.
- Increased vigilance for opportunistic infections and second primary malignancies is needed in ruxolitinib-treated myelofibrosis patients 2.
- Management of cytopenias and infections in patients with myelofibrosis treated with ruxolitinib requires careful investigation and management to optimize therapeutic benefit 4.
- Red blood cell transfusion dependence is a common issue during treatment with ruxolitinib, particularly among patients with pre-existing transfusion dependence 6.