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Interactive Case Study | Uncontrolled Polycythemia Vera (PV) | Inadequate Response to Hydroxyurea

This video offers healthcare professionals the opportunity to participate in a clinical treatment challenge. Hematology specialist Dr Harry Erba presents the case of a patient with uncontrolled polycythemia vera despite treatment with hydroxyurea and invites clinicians to select an appropriate treatment strategy.

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Narrator: Case Study: Uncontrolled PV

Inadequate Response to Hydroxyurea


Introduction

Dr Erba: Hello, my name is Harry Erba. I'm a professor of internal medicine at the University of Alabama at Birmingham where I serve as the director of the hematologic malignancies program as well as the associate director of the cancer center for clinical research. For the last 20 years I have been a clinical investigator evaluating novel therapies for people with myeloid neoplasms including the myeloproliferative neoplasms.

Narrator: This promotional presentation is being sponsored by Incyte Corporation.

Dr Erba: We're going to speak about the labeled indication for Jakafi (ruxolitinib) for patients with polycythemia vera who have had either an inadequate response to or are intolerant of hydroxyurea.

Dr Erba: The information that I will present is all consistent with the labeled indication and consistent with FDA regulations.

We will also discuss important safety information regarding Jakafi.


Uncontrolled Polycythemia Vera (PV)

Dr Erba: Now let’s turn to the clinical management of patients with polycythemia vera. There are important goals in our treatment of patients with polycythemia vera. We have known for some decades now that control of the hematocrit to less than 45% is important in this group of patients.

Dr Erba: Now to that end we've typically used phlebotomy to lower the hematocrit to less than 45% as well as the use of aspirin.

We should also remember that the goal of phlebotomy therapy is to make the patient deficient in iron, which in and of itself will have separate symptoms including fatigue, memory loss, trouble sleeping, dysgeusia, mouth ulcerations, restless legs and we know of nail and hair changes. And so the quality of life of patients on phlebotomy therapy who've become iron-deficient can be compromised. And that should be considered.

Dr Erba: We also need to recognize that phlebotomy and aspirin may not do anything to control the myeloproliferative symptoms that are associated with the disease including the symptomatic progressive splenomegaly.

Dr Erba: In patients who are undergoing phlebotomy and receiving low-dose aspirin for their disease, why would we then consider the use of cytoreductive therapy? And I believe there are a number of reasons to do so. One is that it’s been difficult to maintain the hematocrit less than 45% in a patient, and this could be for a variety of reasons including the proliferative nature of the disease and the requirement in some patients for very frequent phlebotomies. Or on the other hand poor compliance of patients with phlebotomy and phlebotomy schedules.

Dr Erba: If a patient has a high risk of thrombosis, many experts in this area will recommend cytoreductive therapy as well.

These are patients over the age of 60 with a prior history of a thrombotic event.

So for these indications we might consider cytoreductive therapy. In the United States we typically use hydroxyurea but interferon alfa is also used.

Dr Erba: But what do we do for patients that we're giving cytoreductive therapy such as hydroxyurea and they have had an inadequate response in one of those features that led to the use of hydroxyurea or they're intolerant of the use of hydroxyurea?

Dr Erba: The European Leukemia Network has developed a set of criteria for defining patients with uncontrolled polycythemia vera despite hydroxyurea therapy. Now it should be pointed out that in these criteria it is stated that patients should receive at least two grams daily of hydroxyurea for at least three months or the maximally tolerated dose of hydroxyurea before declaring treatment failure.

Dr Erba: We can focus on several indicators of resistance. So if patients continue to need phlebotomy to maintain the hematocrit less than 45%. Or if they have leukocytosis with a white count over 10,000 or thrombocytosis with a platelet count over 400,000.

If they have uncontrolled disease-related symptoms, specifically, for example, splenomegaly.

And then finally if they are intolerant of the myelosuppressive nature of hydroxyurea. And so in order to control the hematocrit or control the splenomegaly or control those symptoms you need to use a dose that leads to neutropenia or thrombocytopenia or even anemia that would be a reason for considering some alternative therapy and declaring that hydroxyurea is not going to be effective. There are also non-hematologic toxicities with hydroxyurea that we need to consider such as leg ulcerations and gastrointestinal toxicities.


Patient Case

Dr Erba: Now let's discuss a patient that actually was enrolled on the RESPONSE trial. The RESPONSE trial was a multicenter randomized Phase III study of Jakafi versus best available therapy in patients with polycythemia vera who had either an inadequate response to or were intolerant of hydroxyurea.

Dr Erba: Here we have a 52-year-old male patient with polycythemia vera. He is a smoker, and he's currently being treated for hypertension. He has had polycythemia vera for 10 years and also the disease is JAK2V617F-positive, as we might expect in 95% of patients with polycythemia vera. He's had no prior thromboembolic events… he is on hydroxyurea and he's receiving 500 mg three times a day. However, he continues to require phlebotomy and has had two in the prior six months.

Dr Erba: You can also see his blood counts. He has polycythemia with a hematocrit of 48%. He also has leukocytosis and thrombocytosis.

He actually hasn't had a prior thromboembolic event, which could lead to the question, why is this patient receiving hydroxyurea? He's under 60, no prior thromboembolic events, so by our current definitions not at high risk for a thromboembolic event from his disease.

However, he does have other cardiovascular risk factors and many of us would use cytoreductive therapy in addition to trying to ameliorate the hypertension and getting him to stop smoking as management of his disease.

Dr Erba: For whatever reason he was started on hydroxyurea and he's taking 500 mg three times a day. However, he continues to require phlebotomy and has had two in the last six months. You can see that his hematocrit is now over 45% on the last check and he also has leukocytosis and thrombocytosis.

And there is clinical data to support having the hematocrit less than 45% in order to decrease the risk of thromboembolic events.

I believe it's safe to say based on this data that this patient has inadequate control of his disease on his current regimen.


Clinical Challenge

Dr Erba: The question is what would you do for this patient?


Treatment Approach Choice 1

Narrator: You have chosen to increase the dose of hydroxyurea.

Dr Erba: There's no mention in the case report that he's having intolerance of the therapy.

In fact, we should be optimizing the dose of therapy.

Dr Erba: I believe it would actually be possible to consider an increase in the dose hydroxyurea as long as the patient is tolerating the current dose. And of course you also have to make sure that the patient is being compliant with the three times daily dose. In fact, it’s possible that by giving him this drug three times a day he actually may only be taking it once or twice a day already. I typically would use doses of one to two grams at a time once a day to improve patient compliance.

Dr Erba: Now one way I check for my patient’s compliance with hydroxyurea is by checking the blood counts and if you see a macrocytosis you can be relatively assured that the patient is taking hydroxyurea.

Dr Erba: I believe that a different option for this patient might be to discontinue hydroxyurea and consider Jakafi.


Treatment Approach Choice 2

Narrator: You have chosen to increase the phlebotomy frequency.

Dr Erba: This could be attempted in an effort to maintain the hematocrit less than 45%.

There's also the issue of compliance, and so you should have a conversation with him about anything in his life that might prevent him from increasing the phlebotomy frequency from the two in six months which has been inadequate for controlling the hematocrit.

Dr Erba: And I think it's also important to address the potential for iron deficiency that’s induced by phlebotomy. And so I would ask questions about the patient’s symptoms that could potentially be related to phlebotomy-induced iron deficiency that could be affecting his quality of life.

And then finally keep in mind that with control of the hematocrit by phlebotomy you leave unaddressed the leukocytosis and thrombocytosis.

Dr Erba: I believe that a different option for this patient might be to discontinue hydroxyurea and consider Jakafi.


Treatment Approach Choice 3

Narrator: You have chosen to discontinue hydroxyurea and initiate interferon alfa.

Dr Erba: In some parts of the world this may be the preferred option. In Europe many patients with polycythemia vera are actually treated with interferon alfa. However, in the United States interferon alfa does not have a labeled indication for polycythemia vera, making patient access to this drug difficult.

Dr Erba: Interferon alfa is a cytoreductive therapy that can be used. I personally would not do that in this patient because I am not convinced that this patient is yet received the maximally tolerated dose of hydroxyurea. So it may be possible to go up on the dose of hydroxyurea without switching to a different agent.

Dr Erba: I believe that a different option for this patient might be to discontinue hydroxyurea and consider Jakafi.


Treatment Approach Choice 4

Narrator: You have chosen to discontinue hydroxyurea and initiate Jakafi.

Dr Erba: You've chosen to discontinue hydroxyurea and initiate Jakafi. I do agree with this decision, however I will make a few points. I believe that when we are treating patients for polycythemia vera with hydroxyurea, interferon alfa or Jakafi that it is important to use the maximally tolerated dose of the drug to achieve your goals. This patient is receiving 500 mg three times a day of hydroxyurea. We haven't heard anything about the tolerability of that dose. If the patient is tolerating that dose, and clearly you can see he does not have cytopenias, you could actually consider increasing the dose of hydroxyurea. Of course the concern would be that you may run into other non-hematologic toxicities such as gastrointestinal toxicity from increasing the dose. But that would be something to try before changing to a different therapy.

Dr Erba: However, assuming that this patient is receiving the maximally tolerated dose of hydroxyurea and still has a hematocrit over 45% despite phlebotomy as well as persistent leukocytosis and thrombocytosis, I believe that this is a patient that should be strongly considered for Jakafi and discontinuation of hydroxyurea, based on the results of the RESPONSE trial demonstrating efficacy and safety of the drug in this situation.


RESPONSE: Trial Design

Dr Erba: Let's now review the RESPONSE trial design. The RESPONSE trial was a randomized Phase III study that compared Jakafi to best available therapy for patients with polycythemia vera who were either intolerant of or had an inadequate response to hydroxyurea as defined by the European Leukemia Network.

Dr Erba: Patients had to have a persistent phlebotomy requirement and as well they also had to have measurable splenomegaly by MRI.

Dr Erba: There was a pre-randomization phase where all of the patients were kind of brought to the same starting gate.

Dr Erba: The hematocrit had to be controlled to less than 45%. And then they were randomized between Jakafi 10 milligrams twice daily or best available therapy.

Dr Erba: Now what I find interesting about this clinical trial is that the patients who were randomized to best available therapy, and remember they were intolerant of or had an inadequate response to hydroxyurea—almost 60% stayed on or received hydroxyurea.

Dr Erba: The primary analysis was done at 32 weeks. The primary endpoint was a composite of hematocrit control with freedom from phlebotomy as well as a 35% or more reduction in splenic volume by MRI.

Narrator: More specifically, to achieve the Hematocrit Control endpoint, patients could not become eligible for phlebotomy between weeks 8 and 32. Phlebotomy eligibility was defined as hematocrit >45% that is ≥3 percentage points higher than baseline or hematocrit >48%, whichever was lower.

Dr Erba: The two groups were well matched for age, gender.

Dr Erba: About half of the patients in both groups had resistance to and the other half intolerance of hydroxyurea.

Dr Erba: Many of these patients had prior thromboembolic events.

Dr Erba: As you can see, patients had a hematocrit less than 45% at the time of randomization. However, the median white blood cell count and platelet count were above normal.


RESPONSE: Trial Results

Dr Erba: Twenty-three percent of patients treated with Jakafi achieved the composite endpoint versus only less than 1% of patients on best available therapy.

And in fact, at 48 weeks, 22 of the 25 patients maintained the composite endpoint.

Dr Erba: In terms of hematocrit control …that was achieved in 60% of patients receiving Jakafi versus only 19% of patients on best available therapy. Likewise, for control of splenomegaly with a decrease in splenic volume by 35% or more as measured by MRI, that was achieved in 40% of patients that were receiving Jakafi versus less than 1% of patients on best available therapy.

Dr Erba: Furthermore, Jakafi demonstrated higher rates of complete hematologic remission compared to best available therapy in this population of patients. Remember complete hematologic remission is defined as hematocrit less than 45% without a phlebotomy requirement, white blood cell count less than 10,000 and platelet count less than 400,000.

Dr Erba: Twenty-four percent of patients treated with Jakafi achieved a completely hematologic remission at 32 weeks compared to 8% with best available therapy.

Dr Erba: Now let's look at the durability of the key secondary and the primary endpoints in the RESPONSE trial.

Dr Erba: First of all, 83% of patients who were receiving Jakafi at study entry were still receiving Jakafi at 80 weeks.

Dr Erba: In terms of the composite primary endpoint 76% of patients who had achieved it at 32 weeks were still in that composite endpoint at 80 weeks. Fifty-eight percent of patients who had achieved a complete hematologic remission at 32 weeks maintained it at 80 weeks.

Dr Erba: And if you look at the components of that composite endpoint, hematocrit control and control of splenomegaly, the responses were durable. It was 77% of patients at 80 weeks who had achieved a hematocrit control of 32 weeks were still maintaining it.

And in terms of controlled splenomegaly only one patient was no longer in response at 80 weeks. Ninety-eight percent of patients who had control of splenomegaly at 32 weeks maintained that response by 80 weeks.


Dosing Considerations

Dr Erba: Now let's discuss the appropriate dosing of Jakafi in patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

The starting dose of Jakafi in this patient population is 10 mg twice daily. Now remember the drug is potentially myelosuppressive and so blood counts should be checked frequently at first, every two to four weeks, and as they stabilize as clinically indicated.

Dr Erba: Also remember that the dose of Jakafi should be adjusted based on tolerability and the goals of your therapy.

Dr Erba: Although the starting dose of Jakafi is 10 mg twice daily, remember it's important to optimize the dose of Jakafi to these patients. In the RESPONSE trial in the first eight weeks, 9% of patients required a dose reduction. But it’s also important to remember that 37% of patients in the first eight weeks actually had a dose increase of Jakafi in an effort to actually achieve the goals of therapy.

Dr Erba: Remember as well that Jakafi is cleared by renal-hepatic mechanisms and so patients with renal-hepatic insufficiency should be considered for lower starting doses of Jakafi. Jakafi is metabolized by CYP3A4 and so patients on CYP3A4 inhibitors, strong ones or even the moderately strong CYP3A4 inhibitor fluconazole, should have a lower starting dose if the CYP3A4 inhibitor cannot be stopped.

Dr Erba: The prescribing information for polycythemia vera indicates that you should consider dose reductions of Jakafi based on platelet counts and hemoglobin.

And this should be followed so as to attempt to avoid abrupt discontinuation for a hemoglobin less than eight or a platelet count less than 50,000.

Dr Erba: The dose of Jakafi can be increased in 5 mg twice-daily increments. The maximum dose of Jakafi is 25 mg twice daily. A dose adjustment or dose increase should not be done in the first four weeks and no sooner than every two weeks.

Dr Erba: I would consider a dose increase for my patients up to the maximum dose of 25 mg twice daily if they require and continue to require phlebotomy, if they still have leukocytosis, thrombocytosis, or splenomegaly.

As long as they have appropriate marrow reserve and so their hemoglobin isn't low and their platelets and neutrophils can tolerate a higher dose.

Dr Erba: But remember if the patient has cytopenias you should not go up on the dose. And so in patients who have low ANC or low platelet count this will keep us from going up on the dose in those situations.

A dose adjustment or dose increase should not be done in the first four weeks and no sooner than every two weeks.


ISI

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
  • 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 ruxolitinib treatment for myelofibrosis. 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
  • The three most frequent non‐hematologic adverse reactions (incidence >10%) were bruising, dizziness and headache
  • A dose modification is recommended 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 breast‐feed

Please view Full Prescribing Information.

Thank you

Dr Erba: Thank you for joining me here today…

Image of the video Interactive Case Study - Uncontrolled Polycythemia Vera (PV) Inadequate Response to Hydroxyurea
Interactive Case Study | Uncontrolled Polycythemia Vera (PV) | Inadequate Response to Hydroxyurea

This video offers healthcare professionals the opportunity to participate in a clinical treatment challenge. Hematology specialist Dr Harry Erba presents the case of a patient with uncontrolled polycythemia vera despite treatment with hydroxyurea and invites clinicians to select an appropriate treatment strategy.

Image of Dr Harry Erba from the video Efficacy and Safety of Jakafi® (ruxolitinib) from the RESPONSE Trial
Efficacy and Safety of Jakafi® (ruxolitinib) From the RESPONSE* Trial

Dr Harry Erba, Director of the Hematologic Malignancy Program at the University of Alabama, reviews the efficacy and safety of Jakafi® (ruxolitinib) in polycythemia vera (PV). Dr Erba presents evidence from the RESPONSE* trial, which compared Jakafi to best available therapy for patients with PV who were either intolerant of or had an inadequate response to hydroxyurea.

* RESPONSE=Randomized study of Efficacy and Safety in POlycythemia vera with JAK iNhibitor ruxolitinib verSus bEst available care

Image of Dr Harry Erba from the video Uncontrolled Polycythemia Vera (PV) Inadequate Response to Hydroxyurea
Identifying Patients Whose Polycythemia Vera Is Uncontrolled With Hydroxyurea

How could polycythemia vera (PV) be managed in patients with an intolerance of or inadequate response to hydroxyurea? Hematologic malignancy expert Dr Harry Erba presents clinical considerations for identifying and managing such patients. In addition, Dr Erba reviews the data about Jakafi® (ruxolitinib) from the RESPONSE* trial.

* RESPONSE=Randomized study of Efficacy and Safety in POlycythemia vera with JAK iNhibitor ruxolitinib verSus bEst available care

Image from the video Dosing of Jakafi® (ruxolitinib) in Patients With Polycythemia Vera Who Have Had an Inadequate Response to or Are Intolerant of Hydroxyurea
Dosing of Jakafi® (ruxolitinib) in Patients With Polycythemia Vera Who Have Had an Inadequate Response to or Are Intolerant of Hydroxyurea

Hematology specialist Dr Harry Erba discusses the appropriate dosing of Jakafi® (ruxolitinib) in patients with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea. Dr Erba addresses the recommended starting dose, dose reductions based on hemoglobin levels and/or platelet counts, and dose modifications due to insufficient response in PV.

Illustration of Jakafi® (ruxolitinib) targeting hematopoietic cell proliferation due to an overactive JAK pathway signaling.
Mechanism of Action of Jakafi® (ruxolitinib)

Hematology specialist Dr Harry Erba reviews the mechanism of action of Jakafi® (ruxolitinib), a JAK1 and JAK2 inhibitor, highlighting how Jakafi works to inhibit overactive JAK pathway signaling. Dr Erba also discusses safety data from the RESPONSE* trial, which compared Jakafi to best available therapy for patients with polycythemia vera who were either intolerant of or had an inadequate response to hydroxyurea.

* RESPONSE=Randomized study of Efficacy and Safety in POlycythemia vera with JAK iNhibitor ruxolitinib verSus bEst available care

Image from the video The Pathogenesis of Polycythemia Vera
The Pathogenesis of Polycythemia Vera

This video illustrates the pathogenesis of polycythemia vera (PV), a myeloproliferative neoplasm that arises from overproduction of hematopoietic stem cells in the bone marrow. The cause of PV is unknown, but may be related to a mutation in the gene coding for the Janus-associated kinase 2 (JAK2) protein. The JAK-STAT pathway helps to regulate normal blood cell production. In PV, the JAK-STAT pathway becomes overactive, leading to an increased number of red blood cells, but overproduction of white blood cells and platelets may also occur. Understanding the cellular origins of PV may lead to further insights into its clinical manifestations, including symptomatology and potential for disease progression.

Jakafi® (ruxolitinib) Efficacy and Safety: The COMFORT* trials

In this video, Salman Fazal, MD, discusses two myelofibrosis clinical trials—the COMFORT I and COMFORT II trials. In addition to reviewing the study design for each, Dr Fazal highlights important efficacy and safety data in these trials. The data show efficacy and safety results of Jakafi® (ruxolitinib) in patients with intermediate-2 risk and high-risk myelofibrosis.

* COMFORT=COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment

Initial Dosing for Jakafi® (ruxolitinib) in Intermediate or High-Risk Myelofibrosis (MF)

Salman Fazal, MD, of the Allegheny Health Network Cancer Institute in Pittsburgh, discusses Jakafi® dosing recommendations in intermediate or high-risk myelofibrosis. Dr Fazal begins by reviewing the recommended starting dose of Jakafi, which is based on a patient’s baseline platelet count. Also discussed are dose modifications, dose reductions, and treatment interruptions for Jakafi in intermediate or high-risk myelofibrosis.

Risk Assessment in Patients With Myelofibrosis (MF)

In this video, Salman Fazal, MD, discusses two commonly employed scoring systems to help estimate prognosis in patients with myelofibrosis (MF)—the International Prognostic Scoring System (IPSS) and Dynamic International Prognostic Scoring System (DIPSS). When evaluated by these risk assessment tools, the majority of patients with MF are found to have either intermediate or high-risk MF. Using IPSS and DIPSS, healthcare providers can accurately determine the risk category of their patients with MF and engage in meaningful discussions about survival and treatment options.

Next: Efficacy and Safety of Jakafi® (ruxolitinib) From the RESPONSE* Trial

INDICATIONS AND USAGE

Jakafi is indicated for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is indicated for treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF.

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 x 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
  • 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
  • The three most frequent non‐hematologic adverse reactions (incidence >10%) were bruising, dizziness and headache
  • A dose modification is recommended 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 two weeks after the final dose

Please see Full Prescribing Information for Jakafi.

 
IMPORTANT SAFETY INFORMATION
 
INDICATIONS AND USAGE
Jakafi is indicated for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is indicated for treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF.
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 x 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
  • 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
  • The three most frequent non‐hematologic adverse reactions (incidence >10%) were bruising, dizziness and headache
  • A dose modification is recommended 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 two weeks after the final dose

Please see Full Prescribing Information for Jakafi.