Hi, my name is Andrew Kuykendall and I'm a malignant hematologist. And today we're going to talk about polycythemia vera. Specifically, we're going to be talking about monitoring blood counts, but also symptom control. I think, symptoms associated with the disease are something that's many times overlooked.

So we know in polycythemia vera it's important to maintain strict hematocrit control less than 45%. And we do that because we know there's risks associated with higher hematocrit levels.

And to make sure we stay in this safe hematocrit zone, say between 40% and 45%, we typically have to intervene slightly below 45% such as 43% or 44%. But in some cases, hydroxyurea and phlebotomy may not be enough to control hematocrit to the levels that I'd like to see.

This is a heavily symptomatic disease and the vast majority of patients experience some sort of symptoms, whether or not they're on hydroxyurea. In fact, up to 80% or more of patients in my practice are symptomatic despite being on hydroxyurea. It’s crucial that I identify and tease out symptoms when I talk to my patients, especially as some symptoms are present before diagnosis and some patients aren’t aware they may be related to their polycythemia vera.

That's why we always take a very focused approach of questioning patients about certain specific symptoms. We'll ask them, "Do you feel like you're having a lot of itching after hot showers? Do you feel very fatigued? Are you waking up with night sweats? Does your partner or family members notice that you're not able to do things that you were able to do 3, 5, 6 years ago? Oftentimes, a light bulb will go off with patients and they'll understand that perhaps these symptoms that they never attributed to their disease really do have an explanation and that can be quite validating.

I also ask patients if family members have noticed any changes in how they feel or in their ability to do things. Family members and caregivers will often notice a change in the patient and may be more willing to talk about it.

In many cases, I'm asking a patient a question and getting a negative answer and looking at the caregiver and they're saying, "Oh no. No. This is something that has been going on." I think that that's really helpful to get a sense for how this disease can impact individual patients.

So, when it comes to PV, it’s important to manage counts and understand the symptoms your patients may be experiencing. The support for using Jakafi in polycythemia vera comes from the RESPONSE trial, and this was a study that showed that Jakafi can help control hematocrit, but there was also an exploratory analysis done in this study that looked very specifically at patient self-reported symptom scores.

RESPONSE was a phase 3 trial that enrolled patients with polycythemia vera who were resistant to, or intolerant of, hydroxyurea. They also required phlebotomy for hematocrit control. The study was designed to look at hematocrit control and reduction in spleen volume of at least 35%. Patients could not become eligible for phlebotomy between weeks 8 and 32 of the trial. And when we look at the composite primary endpoint, you can see that 23% of the patients receiving Jakafi were able to achieve hematocrit control and at least a 35% reduction in spleen volume compared to less than 1% of patients receiving best available therapy.

It was helpful to see that 60% of patients receiving Jakafi achieved hematocrit control. These results demonstrate the efficacy that helps me confidently prescribe Jakafi in appropriate patients who are not achieving strict hematocrit control below 45% despite the maximum tolerated dose of hydroxyurea and phlebotomy.

Data from an exploratory analysis of the RESPONSE trial showed that some patients on Jakafi reported lower total symptom scores at week 32, meaning they perceived their symptoms to have improved from baseline. Specifically, the trial showed that 49% of patients receiving Jakafi had at least a 50% reduction in their MPN-SAF Total Symptom Score.

It's important to keep in mind that response was an open-label trial and it was not designed to evaluate differences in symptoms. Based on an exploratory endpoint, patients receiving Jakafi had reductions in all symptom clusters reported. And when we look at these specific symptom clusters, when we talk about cytokine related symptoms, we're often talking about symptoms such as fatigue, fever, chills, night sweats. And in terms of hyperviscosity symptoms, maybe these are headaches, paresthesias and also symptoms related to splenomegaly. We're often thinking about things like abdominal fullness, early satiety, abdominal pain, discomfort under the ribs.

It's reassuring to know that I have Jakafi for appropriate patients with polycythemia vera. When managing hematocrit I want to keep my patient in the zone between 40 and 45%. And when my patients have elevated hematocrit and disease-related symptoms such as fatigue, pruritus, night sweats at the maximum tolerated dose of hydroxyurea and frequent phlebotomies, I typically intervene with Jakafi.

Let’s take the opportunity to review the safety information for Jakafi.

INDICATIONS AND USAGE

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

• 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
• Herpes zoster infection has been reported in patients receiving Jakafi. Advise patients about early signs and symptoms of herpes zoster and to seek early treatment. Herpes simplex virus reactivation and/or dissemination has been reported in patients receiving Jakafi. Monitor patients for the development of herpes simplex infections. If a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment with Jakafi; patients should be promptly treated and monitored according to clinical guidelines
• 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 (NMSC) 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
• Another JAK-inhibitor has increased the risk of major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and stroke (compared to those treated with tumor TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Jakafi particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur
• Another JAK-inhibitor has increased the risk of thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. In patients with myelofibrosis (MF) and polycythemia vera (PV) treated with Jakafi in clinical trials, the rates of thromboembolic events were similar in Jakafi and control treated patients. Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately
• Another JAK-inhibitor has increased the risk of lymphoma and other malignancies excluding NMSC (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Jakafi, particularly in patients with a known secondary malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers
• 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 (pathogen not specified) and edema. In chronic graft-versus-host disease, the most common nonhematologic adverse reactions (incidence >20%) were infections (pathogen not specified) and viral infections
• Avoid concomitant use with fluconazole doses greater than 200 mg. Dose modifications may be required when administering Jakafi with fluconazole doses of 200 mg or less, or with strong CYP3A4 inhibitors, 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 for Jakafi.