Current MF Treatments

There are several therapies currently in clinical trial aimes at myelofibrosis. We have compiled a list of myelofibrosis clinical trials:

Myelofibrosis Clinical Trials

Existing treatment options for Myelofibrosis
Each patient with MF may have a different set of symptoms and different treatment requirements. Your doctor can describe available treatments that may be appropriate for you, your symptoms and your specific circumstances. Some people with myelofibrosis may remain symptom free for many years and may not require immediate treatment, but they do need to be monitored over time for any signs or symptoms that may suggest worsening of the disease.

For those with MF that require treatment, Jakafi (ruloxitinib) has recently become the first drug approved by the FDA for treating MF patients. Additionally some medicines approved for other diseases can be used to treat the signs and symptoms of MF. These medicines may not be effective for everyone, and some have potentially serious side effects.

Therapies currently used include the following:

• Jakafi (developed by Incyte; also called ruxolitinib)
The discovery of JAK2 mutations in MF, PV and ET in 2005 has provided a long-sought opportunity to develop more effective, targeted therapies for MPNs. A targeted therapy is one that is designed to be more specific for abnormal cells. In 2011, after years of development and clinical trials, Jakafi (also known as ruloxitinib) became the first FDA-approved drug for treating MF patients. Jakafi is taken orally and inhibits the activity of JAK2 and the related protein JAK1. In clinical trials, Jakafi reduced spleen size, abdominal discomfort, early satiety, bone pain, night sweats and itching in MF patients. Jakafi also reduced the level of “pro-inflammatory cytokines” in the blood, which cause the symptoms of chronic inflammation. The allelic burden of JAK2 V617F (a measure of the number of abnormal cells present) was not significantly reduced and Jakafi does not appear to be a cure for MF. So far, the impact of Jakafi on survival has not been fully established.

Importantly, Jakafi is effective in treating MF patients regardless of whether they harbor a JAK2 mutation, apparently because the JAK1 and JAK2 pathways are important in MF even when there is no JAK2 mutation present. Jakafi inhibits both normal JAK1 and JAK2 and JAK2V617F.

Because Jakafi targets normal JAK1 and JAK2, as well as abnormal JAK2, it may interfere with normal blood cell production and common side effects include thrombocytopenia (reduced platelets) and anemia (reduced red blood cells).

• Allogenic stem cell transplantation (ASCT)
ASCT is the only known potential cure for MF, but is not suitable for many patients due to high risk of complications. In this procedure, if a suitable donor can be found, hematopoietic (blood-forming) stem cells are transferred from the healthy donor to the recipient who has MF, to replace their defective stem cells. Prior to the stem cell infusion, high doses of chemotherapy and or radiation therapy are administered to eradicate the diseased bone marrow.

Importantly, ASCT is appropriate for a relatively small number of people with MF. In general, the risk associated with this treatment rises with age and the presence of other disease conditions which may impair organ function; therefore, in older people who may also have other coexisting health problems, there is a higher risk of death from the procedure. Graft versus host disease (GVHD) is another potentially life-threatening complication of ASCT, where the donor’s stem cells react against the recipient’s healthy tissues.

In the hope of improving the outcome of ASCT in older people, reduced-intensity conditioning regimens are now being administered. These strategies, also known as non-myeloablative or minitranplants, use lower doses of chemotherapy or radiation prior to transplant and are particularly promising for those older individuals who, despite their MF, remain fit, and have good organ function.

In general, the decision to pursue ASCT should involve consideration of the patient’s age, the severity of symptoms, response to other therapies, risk tolerance and the patient’s transplant-related prognostic score (a rough measure of likely success, based on factors specific to the patient and the transplant, including, extent of splenomegaly, number of transfusions and whether the transplant is from a related donor).

A number of other drugs that inhibit JAK2 (“JAK inhibitors”) are currently in clinical trials, including CEP-701 (lestuartinib), TG10138, CYT387 and SB1518. Conclusion of these studies will determine whether these drugs may also be promising for treating MF patients.
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. Examples of ongoing clinical trials include experimental therapies with JAK2 inhibitors. As of the current date, only Jakafi (ruxolitinib) has been FDA approved for MF therapy.

Other therapies are generally used to treat specific symptoms of MF. Below is a list of specific symptoms of MF and available therapeutics used to treat these symptoms:

• Anemia may be treated with corticosteroids, androgens (including danazol and halotestin), thalidomide, lenalidomide, blood transfusions, or erythropoiesis stimulating agents (ESAs).

• Splenomegaly may be treated with Jakafi, hydroxyurea (HU), cladibrine, interferon, or, in severe cases, radiation or splenectomy.

• Risk of thrombosis may be managed with low-dose aspirin therapy or hydroxyurea.

• Extramedullary hematopoiesis may be treated with radiation therapy.

• Constitution symptoms, such as night sweats, pruritus, weight loss and fever may be treated with Jakafi.

Novel therapies/Clinical trials:

• Pomalidomide is a chemical relative of thalidomide and lenalidomide and has been shown to effectively treat anemia in early studies. These “immunomodulating” drugs work in many ways, including targeting 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. Importantly, Pomalidomide does not appear to be effective in treating MF patients who do not have the V617F mutation. Pomalidomide appears to be well tolerated and side effects, while infrequent, can include myelosuppression (decreased blood counts) and neuropathy (nerve problems).

• 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 1/2 clinical trials, Everolimus was well tolerated and able to reduce both spleen size and systemic symptoms.

• 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. “HDAC inhibitors” protect specific organizational marks on DNA, while “hypomethylating agents” remove other organizational marks.

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