Transcript



Narrator: Risk Assessment in Patients With Myelofibrosis
Narrator: Jakafi (ruxolitinib) is indicated for treatment of patients with intermediate or high-risk MF, including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF.
Dr Fazal: My name is Salman Fazal. I’m the Interim Director of Cell Transplantation Program at the Allegheny Health Network Cancer Institute in Pittsburgh. I'm also Assistant Professor at Temple University School of Medicine. And over the last seven years, I have been the investigator for clinical trials involving myeloid-malignancies and with myelofibrosis.
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 Fazal: … In this presentation, we are going to discuss patients with intermediate or high-risk myelofibrosis.
Dr Fazal: The information that I will present is all consistent with labeled indication and consistent with FDA regulations. We will also discuss important safety information regarding Jakafi.
Dr Fazal: Unfortunately, the median survival of myelofibrosis is seven years. For the patient that we are seeing in the office to have a more meaningful discussion about their survival, we have risk assessments tools.
So, there are two tools that we have available, which have been developed by the IWG-MRT. There is IPSS and there is dynamic IPSS. IPSS has to be applied at the time of diagnosis, the dynamic IPSS has the beauty of being applied at any time during the course of their illness.
Dr Fazal: There are five different risk factors to determine if the patient has high-risk disease or not.
We have to look at the blast in the peripheral blood and if the blast is more than one percent it is considered adverse.
In terms of looking at the labs, it is important to see the hemoglobin, if the hemoglobin is less than ten grams per deciliter, that is considered adverse.
It is also important to look at the white count and if the white count is more than 25,000, that is considered adverse.
We look at the age of the patient and if the age of the patient is more than 65, it’s considered as an adverse risk factor. It is important to keep in mind that the median age of myelofibrosis is 67.
The presence of constitutional symptoms is considered as adverse risk factors.
It is important to keep in mind that between the IPSS and the dynamic IPSS, anemia is given different score. In the dynamic IPSS, anemia is given a score of two, however, on the IPSS anemia is given a score of one.
Dr Fazal: If you apply these factors to patients with myelofibrosis, approximately 80 percent of patients has either intermediate or high-risk myelofibrosis.
IPSS help us predict the median survival for patients with myelofibrosis.
Dr Fazal: Based on the IPSS, patients who have low-risk disease, their median survival is 11.25 years.
Patients who have intermediate one-risk disease, their median survival is 7.92 years. And patients who have intermediate two-risk disease, their median survival is 4 years. It is important to keep in mind that the patients who have high-risk disease based on the IPSS, their median survival is 2.25 years.
So, identifying patients who have high-risk disease with median survival of 2.25 years is very helpful to discuss different treatment options for this high-risk group.
Dr Fazal: When I'm seeing patients with myelofibrosis, I tell my fellows to reference the IPSS to accurately determine the risk category of the patients because it is not uncommon to underestimate the risk category of patients with myelofibrosis.
Narrator: The MF Chart Audit Study was a market research study conducted in the first quarter of 2014 on behalf of Incyte Corporation. Physicians were asked to categorize their patients' prognoses at the time of diagnosis based on clinical judgment. Prognosis was subsequently calculated using IPSS based on patient chart data and compared with clinical judgment.
Dr Fazal: In a retrospective study sponsored by Incyte, they looked at 326 patient's chart treated by 106 oncologists, they found that nearly six out of the ten patients had their risk category underestimated by their treating physician. On the other hand, 13% of patients had their risk category overestimated by their treating physician.
Again, it is very important to reference the IPSS and accurately determine the risk category of the patients to have more meaningful discussion about treatment options.

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 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 view Full Prescribing Information.
Dr Fazal: Thank you for joining me here today.

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 prognosis and treatment options.



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Image of Dr. Salman Fazal

Salman Fazal, MD
Allegheny Health Network Cancer Institute

Salman Fazal, MD
Allegheny Health Network Cancer Institute

Salman Fazal, MD
Allegheny Health Network Cancer Institute

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Indications and Usage

Jakafi is indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.

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.

Jakafi is indicated for treatment of steroid‐refractory acute graft‐versus‐host disease (GVHD) in adult and pediatric patients 12 years and older.

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 three most common nonhematologic adverse reactions (incidence >10%) were bruising, dizziness and headache. 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 two weeks after the final dose

Please see Full Prescribing Information for Jakafi.