Narrator: Identifying Patients Whose Polycythemia Vera Has Become Advanced
Narrator: Jakafi (ruxolitinib) is indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.
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 patients in whom polycythemia vera, or PV, has become advanced.
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: While many patients with PV may respond well to standard therapy, in a subset of patients, PV may become advanced despite treatment with hydroxyurea, or HU, at the maximum tolerated dose and phlebotomy, resulting in inadequate disease control. This inadequate disease control may present as an inability to control blood counts and/or burdensome disease-related symptoms.
What are the clinical characteristics of advanced PV? I mentioned blood counts earlier, and the two counts we’ll focus on will be the hematocrit levels and the white blood cell, or WBC, counts.
You’re likely aware that maintaining hematocrit less than 45% is a generally recognized goal in patients with PV.
So, the first component of advanced PV is hematocrit greater than or equal to 45%.
But what about white blood cell counts? We know that PV is a trilineage disorder and that blood cell lines other than the erythroid line can be affected.
For the purposes of identifying advanced PV, we look for a white blood cell count greater than 11 thousand, which is derived from a multivariable time-dependent analysis of the CYTO-PV study. In addition to blood counts, we also consider disease-related symptoms of PV. For example, symptoms related to splenomegaly.
Now we’ll see how these components combine to help characterize PV that has become advanced.
Characteristics of advanced PV are hematocrit greater than or equal to 45% PLUS white blood cell count greater than 11 thousand x 109/L OR disease-related symptoms (for example, eg, splenomegaly).
These characteristics may occur in a subset of patients with PV despite treatment with hydroxyurea at the maximum tolerated dose and phlebotomy.
The National Comprehensive Cancer Network, or NCCN, has included in its treatment guidelines a group of factors that may warrant a change in cytoreductive therapy.
- Intolerance or resistance to hydroxyurea or interferon
- Disease-related symptoms
- New thrombosis or disease-related major bleeding
- Frequent and/or persistent need for phlebotomy, but with poor tolerance of phlebotomy, and
When you consider a change in cytoreductive therapy, ruxolitinib (Jakafi) is one option that is included in the NCCN Guidelines.
There are a few things to note in the context of the NCCN Guidelines.
Jakafi is FDA approved for use in PV in patients with an inadequate response to or intolerance of hydroxyurea.
The phase 3 RESPONSE study, which compared Jakafi to best available therapy, included patients with inadequate response defined to include the maximum tolerated dose of hydroxyurea, not just the European LeukemiaNet, or ELN criteria of 2 grams per day, after 3 months.
RESPONSE was an open-label trial and therefore was not designed to evaluate a difference in symptoms.
The clinical effect of Jakafi on thrombosis has not been established.
In a subset of patients, PV may become advanced despite treatment with hydroxyurea at the maximum tolerated dose and phlebotomy.
Clinical characteristics of advanced PV may include hematocrit greater than or equal to 45% PLUS white blood cell WBC count greater than 11 thousand x 109/L OR disease-related symptoms (for example, splenomegaly).
It is important to proactively identify characteristics of advanced PV.
Let’s take the opportunity to 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 advanced PV on the Patient Identification page on the Jakafi website.