What Are the Available Treatments for MF?
There is no single treatment that is effective for all MF sufferers. Each patient has a unique set of symptoms and circumstances that require different treatment options, as prescribed by a doctor. Also, some patients with MF remain symptom-free for many years and may not require immediate treatment. However, anyone who has been diagnosed with MF needs to be monitored over time for signs or symptoms that suggest the disease has worsened.
Available treatments and therapies for MF include:
Jakafi (ruxolitinib) is the first drug approved by the FDA for treating MF patients. Jakafi is indicated for the treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MFAs a targeted therapy, Jakafi is designed to be more specific for abnormal cells. Taken orally, Jakafi partially inhibits the activity of JAK2 and the related protein JAK1. During clinical trials, it was shown to reduce spleen size, abdominal discomfort, early satiety, bone pain, night sweats and itching in MF patients as well as the level of “pro-inflammatory cytokines” in the blood, which may cause some symptoms such as fatigue, fever, night sweats, and weight loss. Patients are observed for low blood counts, headache, dizziness, bruising, or infection. For more about Jakafi, visit the manufacturer’s website.
INREBIC (fedratinib) is indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF). The endpoints focused on the spleen size reduction and symptom relief. It is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). Abnormal activation of JAK2 is associated with myeloproliferative neoplasms, including myelofibrosis and polycythemia vera. According to Celgene, INREBIC does more to inhibit the JAK2-selective mutation than the other JAK family members JAK1, JAK3, and TYK2.
VONJO (Pacritinib) is indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L. This indication is approved under accelerated approval based on spleen volume reduction. Pacritinib is an oral kinase inhibitor with activity against wild type Janus Associated Kinase 2 (JAK2), mutant JAK2V617F form and FMS-like tyrosine kinase 3 (FLT3), which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. The recommended dosage of VONJO is 200 mg orally twice daily. VONJO is the first approved therapy that specifically addresses the needs of patients with cytopenic myelofibrosis.
- Allogenic Stem Cell Transplantation (ASCT)
Allogenic Stem Cell Transplantation is the only curative treatment for MF. ASCT, hematopoietic (blood-forming) stem cells are transferred from a donor to the patient, essentially replacing defective stem cells with healthy ones. Before the stem cell infusion, the patient receives chemotherapy and/or radiation therapy to eradicate diseased bone marrow. In an effort to improve stem cell transplant outcomes for MF patients, MPNRF created a Stem Cell Transplant Timing Tool. The SSTT is a portable on-line tool based on a clinically validated scale. It provides a color signal in response to information entered by a patient, that indicates a risk level and median survival times without a stem cell transplant. A patient can then take what they’ve learned and use it to facilitate a meaningful dialogue between themselves and their physician about their treatment options.
SCT Spectrum Transplant Timing tool is available for free on a mobile phone, tablet and PC. Learn more and evaluate your risk level today.
In many cases, therapies for MF patients target specific signs. These signs and related treatments can include:
- Anemia may be treated with corticosteroids, androgens (including danazol and halotestin), thalidomide, lenalidomide, blood transfusions, or erythropoiesis stimulating agents (ESAs). There are also some drugs currently in clinical trial that aim to improve anemia for people with myelofibrosis.
- Splenomegaly may be treated with Jakafi, hydroxyurea (HU), cladibrine, interferon, or, in severe cases when drug therapy has failed, radiation or splenectomy.
- The risk of thrombosis may be managed with low-dose aspirin therapy or hydroxyurea.
- Non-liver and spleen extramedullary hematopoiesis may be treated with radiation therapy.
- Constitutional symptoms, such as night sweats, pruritus, weight loss, and fever may be treated with Jakafi.
Novel Approaches and Clinical Trials
For many patients with MF, available treatment approaches may not be effective, and experimental treatments (which involve receiving a novel drug or treatment on a clinical trial), may be an appropriate option.
There are many novel therapies currently in clinical trial, including multiple mechanisms of action:
A number of other drugs that inhibit JAK2 (“JAK inhibitors”) are currently in clinical trials.
Epigenetic drugs change the way genes are organized to make them more or less accessible for use by the cell. Recent studies with epigenetic drugs have found that the HDAC inhibitor, Givinostat, and two hypomethylating agents, azacitidine and decitabine, were minimally effective in treating MF in early studies (in contrast to their effectiveness in treating PV). Another HDAC inhibitor, panobinostat, is under study.
Pomalidomide has been shown to effectively treat anemia in early studies. It targets the patient’s immune system to attack abnormal cells in order to make room for the normal cells that make red blood cells. With enhanced anti-cancer activity and lower toxicity compared to the other drugs in its class, pomalidomide has shown promise in initial studies and is now in phase 3 clinical trials for its use as first line therapeutic for treating anemia in MF patients who have the V617F mutation.
Everolimus (also known as RAD001) is an inhibitor of the mTOR/AKT pathway, which is highly active in MF blood producing cells and appears to contribute to abnormal cell growth. In phase 1 and 2 clinical trials, Everolimus was well tolerated and able to reduce both spleen size and systemic symptoms.
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