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Myelofibrosis: patients on Ruxolitinib experience a reduction in spleen size that is maintained over time and a clinically meaningful improvement in symptoms

Data from the largest clinical trial of myelofibrosis patients treated with Ruxolitinib ( Jakavi ) were presented at 56th Annual Meeting of the American Society of Hematology ( ASH ) in San Francisco ( California, US ), and have supported the safety profile and efficacy benefit as measured in primary and secondary endpoints respectively.
In an analysis of 1,144 patients treated with Ruxolitinib, 69% of patients achieved more than 50% reduction in spleen size from baseline and patients also experienced a clinically meaningful improvement in myelofibrosis symptom score, important treatment goals for patients with myelofibrosis.

The JUMP study is a phase IIIb, expanded-access trial for countries with no access to Ruxolitinib outside of a clinical trial. The open-label, multicenter study analyzed 1,144 enrolled myelofibrosis patients who received daily starting doses of either 5 mg, 15 mg or 20 mg of Ruxolitinib twice daily based on platelet counts at baseline.
The primary endpoint is assessment of safety and tolerability of Ruxolitinib.
Additional analyses included changes in spleen size and symptom scores as measured by the FACT-Lymphoma Total Score ( FACT-Lym TS ).

Overall, the safety and efficacy profile of Ruxolitinib was consistent with previous studies. The most common grade 3 or 4 hematologic adverse events were anemia ( 33.0% ) and thrombocytopenia ( 12.5% ); however, they rarely led to discontinuation ( 2.6% of discontinuation was due to anemia and 3.2% of discontinuation was due to thrombocytopenia ).
The most common nonhematologic adverse reactions were diarrhea ( 14.5% ), fever ( 13.3% ), fatigue ( 12.9% ) and asthenia ( 12.5% ), which were primarily grade 1 or 2.

Ruxolitinib is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases and was approved by the European Commission in August 2012 for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis ( also known as chronic idiopathic myelofibrosis ), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.
The recommended starting dose for Ruxolitinib in patients with myelofibrosis is 15 mg twice daily for patients with a platelet count between 100,000 cubic millimeters ( mm3) and 200,000 mm3, and 20 mg twice daily for patients with a platelet count of more than 200,000 mm3. Doses may be titrated based on safety and efficacy.
There is limited information to recommend a starting dose for patients with platelet counts between 50,000/mm3 and less than 100,000/mm3. The maximum recommended starting dose in these patients is 5 mg twice daily, and patients should be titrated cautiously.

Myelofibrosis is a rare, life-threatening blood cancer, with approximately 1 in every 133,000 people estimated to be affected by the disease.
Myelofibrosis develops when uncontrolled signaling in the JAK pathway, which regulates blood cell production, causes the body to make blood cells that do not work properly, which scars the bone marrow and results in an enlarged spleen as well as other severe complications and debilitating symptoms.
Studies have shown that patients with myelofibrosis have a decreased life expectancy, with a median overall survival of 5.7 years.
Although allogeneic stem cell transplantation may cure myelofibrosis, the procedure is associated with significant morbidity and transplant-related mortality and is available to less than 5% of patients who are young and fit enough to undergo the procedure.
Current myelofibrosis treatment strategies are aimed at reducing spleen size, relieving symptoms, improving quality of life and reducing the risk of complications. ( Xagena )

Source: Novartis, 2014