For adults with intermediate- or high-risk MF1

At diagnosis, intervene with Jakafi® (ruxolitinib): A treatment with 5-year overall survival data1-4

COMFORT-I primary endpoint*

42%

of patients receiving Jakafi achieved a ≥35% reduction in spleen volume at week 24 vs 0.7% of patients receiving placebo (P<0.0001)1,5

  • 4.4 years median duration of spleen response among primary responders (n=65)2†
  • 99% of patients experienced some reduction in spleen volume on Jakafi5,6

COMFORT-I 5-year OS analysis‡: Jakafi and placebo

  • At 3 years, survival probability was 70% for patients originally randomized to Jakafi and 61% for those originally randomized to placebo1
  • OS was a prespecified secondary endpoint in COMFORT-I1

OS Kaplan-Meier Curves by Treatment Group in COMFORT-I1-3,a

OS KM Curve Comfort-I
All patients in the placebo group either crossed over to Jakafi at a median of 9 months or discontinued.1
 
aCOMFORT-I was not designed to compare survival probabilities between Jakafi and placebo at 3 or 5 years.2
bPatients randomized to placebo were eligible to cross over to receive Jakafi because of progression-driven events or at the physician's discretion; however, these patients continued to be grouped within their original randomized assignment for analysis purposes.2
Dr Ruben Mesa

As a clinician, I want a therapy that can meet my treatment goals. And seeing the impact of Jakafi on spleen volume reduction and overall survival gives me the confidence to intervene with Jakafi at diagnosis, instead of watching and waiting.

HEAR MORE ABOUT SVR AND OS FROM DR MESA

COMFORT-II primary endpoint§

29%

of patients receiving Jakafi achieved a ≥35% reduction in spleen volume at week 48 vs 0% of patients receiving BAT‖ (P<0.0001)1,7

COMFORT-II 5-year OS analysis‡: Jakafi and BAT

  • At 3 years, survival probability was 79% for patients originally randomized to Jakafi and 59% for those originally randomized to BAT1
  • OS was a prespecified secondary endpoint in COMFORT-II1

OS Kaplan-Meier Curves by Treatment Group in COMFORT-II1,4,a

OS KM Curve Comfort-II
All patients in the BAT group either crossed over to Jakafi at a median of 17 months or discontinued.1
 
aCOMFORT-II was not designed to compare survival probabilities between Jakafi and BAT at 3 or 5 years.2
bPatients randomized to BAT were eligible to cross over to receive Jakafi because of progression-driven events or at the physician's discretion; however, these patients continued to be grouped within their original randomized assignment for analysis purposes.2
Dr Salman Fazal

I do not use hydroxyurea for my myelofibrosis patients. The overall survival data available from COMFORT studies give me the confidence of prescribing Jakafi for my appropriate patients at diagnosis and not to delay the treatment.

HEAR HOW DR FAZAL APPROACHES ACTIVE MANAGEMENT
EARLIER VS LATER
INTERVENTION REVIEW JUMP STUDY EXPLORE SAFETY DATA
*COMFORT-I was a randomized, double-blind, placebo-controlled phase 3 study with 309 patients with intermediate-2-risk or high-risk MF. The primary endpoint was the proportion of patients achieving a ≥35% reduction in spleen volume from baseline to week 24 as measured by CT or MRI.1,5
†Duration of spleen response was defined as the interval between the first spleen response measurement that was a ≥35% reduction from baseline and the date of the first measurement that was no longer a ≥35% reduction from baseline that was also a >25% increase from nadir.2
‡The 5-year OS analysis is not included in the Full Prescribing Information for Jakafi. Although the 3-year OS analysis is presented in the Full Prescribing Information, P values and HRs are omitted from the OS Kaplan-Meier curves.2
§COMFORT-II was a randomized, open-label phase 3 study with 219 patients with intermediate-2-risk or high-risk MF. The primary endpoint was the proportion of patients achieving a ≥35% reduction in spleen volume from baseline at week 48 as measured by CT or MRI.1,4
‖BAT in COMFORT-II included hydroxyurea (46.6%) and glucocorticoids (16.4%), as well as no medication, anagrelide, epoetin alfa, thalidomide, lenalidomide, mercaptopurine, thioguanine, danazol, peginterferon alfa-2a, interferon-α, melphalan, acetylsalicylic acid, cytarabine, and colchicine.2
BAT=best available therapy; COMFORT=COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment; CT=computed tomography; HR=hazard ratio; JUMP=JAK Inhibitor RUxolitinib in Myelofibrosis Patients; MF=myelofibrosis; MRI=magnetic resonance imaging; OS=overall survival; SVR=spleen volume reduction.

References: 1. Jakafi [package insert]. Wilmington, DE: Incyte Corporation. 2. Data on file. Incyte Corporation. Wilmington, DE. 3. Verstovsek S, Mesa RA, Gotlib J, et al; for the COMFORT-I investigators. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017;10(1):55. 4. Harrison CN, Vannucchi AM, Kiladjian J-J, et al; on behalf of the COMFORT-II Investigators. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016;30(8):1701-1707. 5. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799-807. Supplementary appendix available at: https://www.nejm.org/doi/full/10.1056/nejmoa1110557. 6. Deisseroth A, Kaminskas E, Grillo J, et al. US Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Clin Cancer Res. 2012;18(12):3212-3217. 7. Harrison C, Kiladjian J-J, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787-798.

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INDICATIONS AND USAGE

JAKAFI®/JAKAFI XR™ (ruxolitinib) is for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF in adults.

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

JAKAFI/JAKAFI XR is for treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in adult and pediatric patients 12 years and older.

JAKAFI/JAKAFI XR is for treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia, Anemia and Neutropenia

  • JAKAFI/JAKAFI XR can cause dose-related effects of thrombocytopenia, anemia and neutropenia. 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/JAKAFI XR. Platelet transfusions may be necessary.
  • Patients developing anemia may require blood transfusions and/or dose modifications of JAKAFI/JAKAFI XR.
  • Severe neutropenia (ANC <0.5 × 109/L) was generally reversible by withholding JAKAFI/JAKAFI XR until recovery.

Risk of Infection

Tuberculosis

  • Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting JAKAFI/JAKAFI XR until active serious infections have resolved. Observe patients receiving JAKAFI/JAKAFI XR for signs and symptoms of infection and manage promptly.
  • Tuberculosis (TB) infection with JAKAFI/JAKAFI XR has been reported. Observe patients taking JAKAFI/JAKAFI XR for signs and symptoms of active TB and manage promptly. Prior to initiating, 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 in patients with evidence of active or latent TB. Continuation during treatment of active TB should be based on the overall risk-benefit determination.

Progressive Multifocal Leukoencephalopathy

  • Progressive multifocal leukoencephalopathy (PML) has occurred with JAKAFI/JAKAFI XR treatment. If PML is suspected, stop JAKAFI/JAKAFI XR and evaluate.

Herpes Zoster and Herpes Simplex

  • Herpes zoster infection, reactivation and/or dissemination has been reported in patients receiving JAKAFI/JAKAFI XR. Advise patients about early signs and symptoms of herpes zoster and seek treatment. Monitor patients for the development of herpes simplex infections. If a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment.

Hepatitis B

  • 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.

Symptom Exacerbation Following Interruption or Discontinuation of Treatment

  • When discontinuing JAK-Inhibitors, including JAKAFI/JAKAFI XR, myeloproliferative neoplasm-related signs and symptoms may flare. After discontinuation, some patients with myelofibrosis have experienced fever, respiratory distress, hypotension, disseminated intravascular coagulation (DIC), or multi-organ failure. If any of these occur after discontinuation or while tapering JAKAFI/JAKAFI XR, evaluate and treat any intercurrent illness and consider restarting or increasing the dose. Instruct patients not to interrupt or discontinue JAKAFI/JAKAFI XR without consulting their physician. When discontinuing or interrupting JAKAFI/JAKAFI XR for reasons other than life-threatening toxicities, consider gradual tapering rather than abrupt discontinuation.

Non-Melanoma Skin Cancer (NMSC)

  • NMSC including basal cell, squamous cell, and Merkel cell carcinoma have occurred. Perform periodic skin examinations.

Lipid Elevations

  • Treatment with JAKAFI/JAKAFI XR has been associated with increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Assess lipid parameters 8-12 weeks after initiation.

Major Adverse Cardiovascular Events (MACE)

  • 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 TNF blockers), in patients with rheumatoid arthritis, a condition for which JAKAFI/JAKAFI XR is not indicated. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy, 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.

Thrombosis

  • 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/JAKAFI XR is not indicated. In patients with myelofibrosis (MF) and polycythemia vera (PV), the rates of thromboembolic events were similar in JAKAFI/JAKAFI XR and control treated patients. Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately.

Secondary Malignancies

  • 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/JAKAFI XR is not indicated. Patients who are current or past smokers are at additional increased risk.

Adverse Reactions

  • In myelofibrosis, the most common hematologic adverse reactions (incidence >20%) were thrombocytopenia and anemia. The most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache and diarrhea.
  • In polycythemia vera, the most common hematologic adverse reactions (incidence >20%) were thrombocytopenia and anemia. The most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache and diarrhea.
  • In acute graft-versus-host disease, the most common hematologic adverse reactions (incidence >50%) were anemia, thrombocytopenia and neutropenia. The most common nonhematologic adverse reactions (incidence >50%) were infections (pathogen not specified) and edema.
  • In chronic graft-versus-host disease, the most common hematologic adverse reactions (incidence >35%) were anemia and thrombocytopenia. The most common nonhematologic adverse reactions (incidence ≥20%) were infections (pathogen not specified) and viral infections.

Drug Interactions

  • Avoid concomitant use with fluconazole doses greater than 200 mg. Dose modifications may be required when administering 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.

Pregnancy

  • Use during pregnancy is not recommended and should only be used if the potential benefit justifies the potential risk to the fetus. Women taking JAKAFI/JAKAFI XR should not breastfeed during treatment and for 2 weeks after the final dose.

Please see Full Prescribing Information for JAKAFI and JAKAFI XR.

INDICATIONS AND USAGE

JAKAFI®/JAKAFI XR™ (ruxolitinib) is for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF in adults.

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

JAKAFI/JAKAFI XR is for treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in adult and pediatric patients 12 years and older.

JAKAFI/JAKAFI XR is for treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia, Anemia and Neutropenia

  • JAKAFI/JAKAFI XR can cause dose-related effects of thrombocytopenia, anemia and neutropenia. 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/JAKAFI XR. Platelet transfusions may be necessary.
  • Patients developing anemia may require blood transfusions and/or dose modifications of JAKAFI/JAKAFI XR.
  • Severe neutropenia (ANC <0.5 × 109/L) was generally reversible by withholding JAKAFI/JAKAFI XR until recovery.

Risk of Infection

Tuberculosis

  • Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting JAKAFI/JAKAFI XR until active serious infections have resolved. Observe patients receiving JAKAFI/JAKAFI XR for signs and symptoms of infection and manage promptly.
  • Tuberculosis (TB) infection with JAKAFI/JAKAFI XR has been reported. Observe patients taking JAKAFI/JAKAFI XR for signs and symptoms of active TB and manage promptly. Prior to initiating, 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 in patients with evidence of active or latent TB. Continuation during treatment of active TB should be based on the overall risk-benefit determination.

Progressive Multifocal Leukoencephalopathy

  • Progressive multifocal leukoencephalopathy (PML) has occurred with JAKAFI/JAKAFI XR treatment. If PML is suspected, stop JAKAFI/JAKAFI XR and evaluate.

Herpes Zoster and Herpes Simplex

  • Herpes zoster infection, reactivation and/or dissemination has been reported in patients receiving JAKAFI/JAKAFI XR. Advise patients about early signs and symptoms of herpes zoster and seek treatment. Monitor patients for the development of herpes simplex infections. If a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment.

Hepatitis B

  • 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.

Symptom Exacerbation Following Interruption or Discontinuation of Treatment

  • When discontinuing JAK-Inhibitors, including JAKAFI/JAKAFI XR, myeloproliferative neoplasm-related signs and symptoms may flare. After discontinuation, some patients with myelofibrosis have experienced fever, respiratory distress, hypotension, disseminated intravascular coagulation (DIC), or multi-organ failure. If any of these occur after discontinuation or while tapering JAKAFI/JAKAFI XR, evaluate and treat any intercurrent illness and consider restarting or increasing the dose. Instruct patients not to interrupt or discontinue JAKAFI/JAKAFI XR without consulting their physician. When discontinuing or interrupting JAKAFI/JAKAFI XR for reasons other than life-threatening toxicities, consider gradual tapering rather than abrupt discontinuation.

Non-Melanoma Skin Cancer (NMSC)

  • NMSC including basal cell, squamous cell, and Merkel cell carcinoma have occurred. Perform periodic skin examinations.

Lipid Elevations

  • Treatment with JAKAFI/JAKAFI XR has been associated with increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Assess lipid parameters 8-12 weeks after initiation.

Major Adverse Cardiovascular Events (MACE)

  • 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 TNF blockers), in patients with rheumatoid arthritis, a condition for which JAKAFI/JAKAFI XR is not indicated. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy, 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.

Thrombosis

  • 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/JAKAFI XR is not indicated. In patients with myelofibrosis (MF) and polycythemia vera (PV), the rates of thromboembolic events were similar in JAKAFI/JAKAFI XR and control treated patients. Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately.

Secondary Malignancies

  • 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/JAKAFI XR is not indicated. Patients who are current or past smokers are at additional increased risk.

Adverse Reactions

  • In myelofibrosis, the most common hematologic adverse reactions (incidence >20%) were thrombocytopenia and anemia. The most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache and diarrhea.
  • In polycythemia vera, the most common hematologic adverse reactions (incidence >20%) were thrombocytopenia and anemia. The most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache and diarrhea.
  • In acute graft-versus-host disease, the most common hematologic adverse reactions (incidence >50%) were anemia, thrombocytopenia and neutropenia. The most common nonhematologic adverse reactions (incidence >50%) were infections (pathogen not specified) and edema.
  • In chronic graft-versus-host disease, the most common hematologic adverse reactions (incidence >35%) were anemia and thrombocytopenia. The most common nonhematologic adverse reactions (incidence ≥20%) were infections (pathogen not specified) and viral infections.

Drug Interactions

  • Avoid concomitant use with fluconazole doses greater than 200 mg. Dose modifications may be required when administering 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.

Pregnancy

  • Use during pregnancy is not recommended and should only be used if the potential benefit justifies the potential risk to the fetus. Women taking JAKAFI/JAKAFI XR should not breastfeed during treatment and for 2 weeks after the final dose.

Please see Full Prescribing Information for JAKAFI and JAKAFI XR.