From the Guidelines
Ruxolitinib is the primary target to reduce splenomegaly in primary myelofibrosis.
Key Points
- Ruxolitinib is recommended as first-line therapy for MF-associated splenomegaly in patients with intermediate-2 or high-risk disease 1.
- In patients with intermediate-1 risk disease and highly symptomatic splenomegaly, ruxolitinib is also recommended as first-line therapy 1.
- Ruxolitinib acts by inhibiting dysregulated JAK-STAT signalling, present in all MF patients, and is indicated in both JAK2-mutated and JAK2-unmutated MF 1.
- The drug has been shown to reduce spleen volume and improve symptoms in MF patients, with a survival advantage compared to placebo or best available therapy 1.
- Some key considerations when using ruxolitinib include the risk of thrombocytopaenia, worsening anaemia, and infection, as well as the potential for a shock-like syndrome with sudden withdrawal 1.
Treatment Approach
- For patients with low-risk disease or intermediate-1 risk disease without highly symptomatic splenomegaly, hydroxyurea may be considered as first-line therapy 1.
- Ruxolitinib is also recommended for patients who do not respond or are intolerant to hydroxyurea 1.
From the Research
Target for Reducing Splenomegaly in Primary Myelofibrosis
The target for reducing splenomegaly in primary myelofibrosis is the Janus kinase (JAK) pathway, specifically the JAK2 inhibitor.
- JAK2 inhibitors, such as ruxolitinib, have been shown to be effective in reducing splenomegaly and improving symptoms in patients with primary myelofibrosis 2, 3, 4, 5.
- The JAK2 inhibitor ruxolitinib was approved by the US Food and Drug Administration in 2011 for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis 2.
- Other JAK inhibitors, such as fedratinib, have also been approved for the treatment of myelofibrosis and have shown efficacy in reducing splenomegaly and symptom burden 5.
Mechanism of Action
The JAK2 inhibitors work by inhibiting the JAK2 pathway, which is involved in the signaling of cytokines and growth factors that promote cell proliferation and survival.
- The JAK2V617F mutation is present in approximately 50-60% of patients with primary myelofibrosis and is associated with the development of splenomegaly and other symptoms of the disease 2.
- Inhibition of the JAK2 pathway has been shown to reduce splenomegaly and improve symptoms in patients with primary myelofibrosis by decreasing the proliferation of malignant cells and reducing the production of pro-inflammatory cytokines 6, 3, 4, 5.
Clinical Benefits
The use of JAK2 inhibitors has been shown to have several clinical benefits in patients with primary myelofibrosis, including: