Narrator: Risk Factors and Splenomegaly in Myelofibrosis (MF)
Jakafi (ruxolitinib) is indicated for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF in adults.
Important Safety Information is discussed later in this video.
Dr Grad: Hi. I’m Dr Gary Grad, a hematologist-oncologist in private practice in the Chicago area. Patients with myeloproliferative neoplasms, or MPNs, form an important part of my practice, and I’m happy to be able to talk to you today about risk factors and splenomegaly in patients with MF.
Narrator: This promotional presentation is being sponsored by Incyte Corporation.
The speaker is presenting on behalf of, and is being compensated by, Incyte Corporation.
Dr Grad: As you may know, there are prognostic scoring systems for patients with MF that use risk factors to generate a score that can then be used to classify disease as low, intermediate or high risk.
Some practitioners use these systems regularly, but some choose instead to use direct clinical assessment.
Of interest, the 8 risk factors from the Dynamic International Prognostic Scoring System Plus tool, or DIPSS Plus, may provide insight even without generating a formal score.
Based on the DIPSS Plus scoring system, if any one of the 8 risk factors is present in a patient with MF, this patient is already intermediate risk. Presence of any additional risk factors may raise the patient’s risk level to high risk.
Constitutional symptoms are weight loss greater than 10% of the baseline value in the year preceding primary MF diagnosis and/or unexplained fever or excessive sweats persisting for more than 1 month.
Note, there are several cytogenetic abnormalities mutations that are included under unfavorable karytotype, as listed on this screen.
In fact, in a study of patients with primary MF, approximately 90%, 375 of 428, of evaluable patients were considered to be intermediate or high risk within 1 year of diagnosis of MF.
So, even without choosing to complete a formal score, you can identify patients who are already intermediate risk by the presence of at least one of these risk factors.
One interesting aspect of the scoring systems for MF is that they allow for estimation of prognosis.
For example, the International Prognostic Scoring System, or IPSS, which is used to assess patients at the time of diagnosis of MF, provides projected life expectancy for patients with low-, intermediate-1, intermediate-2, and high-risk disease. As you can see from the graph, each step up in risk level has implications for diminished life expectancy, with a fairly significant drop from low risk to high risk.
These data help underscore that MF is a serious hematologic malignancy.
Let’s switch gears and look at a risk factor not included in the scoring systems, namely splenomegaly.
In a study of 1,054 patients with primary MF, approximately 90% of patients for whom data were available had palpable splenomegaly at diagnosis.
Therefore, let’s consider the following: What is the clinical significance of splenomegaly in patients with MF? And, is splenomegaly associated with clinical issues or outcomes of concern?
Response criteria from the International Working Group-Myeloproliferative Neoplasms Research and Treatment, or IWG-MRT, and the European LeukemiaNet, or ELN, state that a palpable spleen of greater than or equal to 5 cm below the left costal margin constitutes progressive disease.
Other concerns from splenomegaly include symptom burden, such as pain, early satiety, and abdominal fullness or discomfort, as well as other symptoms, and cytopenias from splenic sequestration of blood cells.
Narrator: Jakafi is indicated for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF in adults.
Dr Grad: In patients with any one of the risk factors shown earlier, MF has already reached intermediate risk.
Splenomegaly may be an indicator of disease progression and can be associated with symptom burden and cytopenias.
Now let’s review safety information for Jakafi.
Narrator: Important Safety Information
- Treatment with Jakafi® (ruxolitinib) can cause thrombocytopenia, anemia and neutropenia, which are each dose‐related effects. Perform a pre‐treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated
- Manage thrombocytopenia by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary
- Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi
- Severe neutropenia (ANC <0.5 × 109/L) was generally reversible by withholding Jakafi until recovery
- Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting Jakafi until active serious infections have resolved. Observe patients receiving Jakafi for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines
- Tuberculosis (TB) infection has been reported. Observe patients taking Jakafi for signs and symptoms of active TB and manage promptly. Prior to initiating Jakafi, evaluate patients for TB risk factors and test those at higher risk for latent infection. Consult a physician with expertise in the treatment of TB before starting Jakafi in patients with evidence of active or latent TB. Continuation of Jakafi during treatment of active TB should be based on the overall risk‐benefit determination
- Progressive multifocal leukoencephalopathy (PML) has occurred with Jakafi treatment. If PML is suspected, stop Jakafi and evaluate
- Advise patients about early signs and symptoms of herpes zoster and to seek early treatment
- Increases in hepatitis B viral load with or without associated elevations in alanine aminotransferase and aspartate aminotransferase have been reported in patients with chronic hepatitis B virus (HBV) infections. Monitor and treat patients with chronic HBV infection according to clinical guidelines
- When discontinuing Jakafi, myeloproliferative neoplasm-related symptoms may return within one week. After discontinuation, some patients with myelofibrosis have experienced fever, respiratory distress, hypotension, DIC, or multi‐organ failure. If any of these occur after discontinuation or while tapering Jakafi, evaluate and treat any intercurrent illness and consider restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafi without consulting their physician. When discontinuing or interrupting Jakafi for reasons other than thrombocytopenia or neutropenia, consider gradual tapering rather than abrupt discontinuation
- Non‐melanoma skin cancers including basal cell, squamous cell, and Merkel cell carcinoma have occurred. Perform periodic skin examinations
- Treatment with Jakafi has been associated with increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Assess lipid parameters 8-12 weeks after initiating Jakafi. Monitor and treat according to clinical guidelines for the management of hyperlipidemia
- In myelofibrosis and polycythemia vera, the most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache, and diarrhea. In acute graft-versus-host disease, the most common nonhematologic adverse reactions (incidence >50%) were infections and edema
- Dose modifications may be required when administering Jakafi with strong CYP3A4 inhibitors or fluconazole or in patients with renal or hepatic impairment. Patients should be closely monitored and the dose titrated based on safety and efficacy
- Use of Jakafi during pregnancy is not recommended and should only be used if the potential benefit justifies the potential risk to the fetus. Women taking Jakafi should not breastfeed during treatment and for 2 weeks after the final dose
Please see Full Prescribing Information.
Dr Grad: Thank you for your time.
You can learn more about risk and myelofibrosis on the Patient Identification page on the Jakafi website.