MF management should focus on achieving 3 key treatment goals, including overall survival1,2

Dr Ruben Mesa, MD, FACP, MPN Expert

When managing patients with MF, my goals include control of the
SPLEEN and SYMPTOMS, with an ultimate goal of OVERALL
SURVIVAL.

When managing patients with MF, my goals include control of the SPLEEN and SYMPTOMS, with an ultimate goal of OVERALL SURVIVAL.

Ruben Mesa, MD, FACP, MPN Expert

Palpable spleen is a marker of disease progression and is associated with poor OS3,4

  • A palpable spleen of ≥5 cm below the left costal margin constitutes progressive disease,† according to the IWG-MRT and ELN response criteria3

Larger baseline spleen volume was associated with incremental increases in the risk of death4

Relationship Between Spleen Volume and Risk of Death in the COMFORT Studies4
Graph of Relationship Between Spleen Volume and Risk of Death

This material is under a CC BY-NC License and is the property of the Ferrata Storti Foundation. © 2023 Ferrata Storti Foundation. All rights reserved.

  • In a post hoc pooled analysis of OS in the COMFORT studies (N=528), there was a 14% increase in the risk of death for each additional 5 dL in spleen volume at baseline over 3 years (HR, 1.14; 95% CI, 1.07-1.21)4‡
  • These increases were seen irrespective of treatment5
Dr Fazal

When my adult patients with intermediate- to high-risk myelofibrosis are experiencing any degree of splenomegaly at diagnosis, that is a sign that I need to intervene with Jakafi.

HEAR WHY DR FAZAL INTERVENES AT DIAGNOSIS
Dr Mesa Spleen Volume Response and OS video

Dr Mesa discusses how early intervention may impact spleen volume and OS

HEAR HIS PERSPECTIVE
EXPLORE SVR AND
5-YEAR OS DATA VIEW ANEMIA ANALYSIS
  • *Data were available for 768 patients, 681 of whom had palpable splenomegaly.5
  • †Progressive disease assignment for splenomegaly requires confirmation by CT or MRI showing a ≥25% increase in spleen volume from baseline. Baseline values for both physical examination and imaging studies refer to pretreatment baseline and not to posttreatment measurements.3
  • ‡A post hoc pooled analysis of OS with ruxolitinib was performed using data from 2 phase 3 studies: COMFORT-I, a randomized, double-blind, placebo-controlled study with 309 patients with intermediate-2-risk or high-risk MF, and COMFORT-II, a randomized, open-label study with 219 patients with intermediate-2-risk or high-risk MF. The primary endpoint in both studies was the proportion of patients achieving a ≥35% reduction in spleen volume (measured by CT or MRI)—at week 24 in COMFORT-I and at week 48 in COMFORT-II.4,6,7

CI=confidence interval; COMFORT=COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment; CT=computed tomography; ELN=European LeukemiaNet; HR=hazard ratio; IWG-MRT=International Working Group-Myeloproliferative Neoplasms Research and Treatment; MF=myelofibrosis; MPN=myeloproliferative neoplasm; MRI=magnetic resonance imaging; OS=overall survival; SVR=spleen volume reduction.

References: 1. Barbui T, Barosi G, Birgegard G, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29(6):761-770. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms V.2.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed June 23, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 3. Tefferi A, Cervantes F, Mesa R, et al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013;122(8):1395-1398. 4. Vannucchi AM, Kantarjian HM, Kiladjian J-J, et al; on behalf of the COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015;100(9):1139-1145. 5. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113(13):2895-2901. 6. 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. 7. 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.

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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.