Image of healthcare professionals discussing Myelofibrosis Clinical Trial Results Image of healthcare professionals discussing Myelofibrosis Clinical Trial Results

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.

Image of texts that says COMFORT-I Primary Endpoint Image of texts that says COMFORT-I Primary Endpoint

4.4 YEARS MEDIAN DURATION OF SPLEEN RESPONSE AMONG PRIMARY RESPONDERS (n=65)3†

Primary Endpoint Results

Image that shows COMFORT-I: Percent Change in Spleen Volume in Individual Patients from Baseline to Week 24 or Last Observation Image that shows COMFORT-I: Percent Change in Spleen Volume in Individual Patients from Baseline to Week 24 or Last Observation

Each bar represents an individual patient's response.
Derived from Verstovsek S et al. N Engl J Med. 2012;366(9):799-807.

of patients experienced some reduction in spleen volume on Jakafi2,4

Most patients receiving placebo experienced an increase in
spleen volume.1,2

Image that shows COMFORT-II Primary Endpoint‡: 29% of patients receiving Jakafi achieved a ≥35% reduction in spleen volume at week 48 vs 0% of patients receiving best available therapy§ (P <0.0001)1,5 Image that shows COMFORT-II Primary Endpoint‡: 29% of patients receiving Jakafi achieved a ≥35% reduction in spleen volume at week 48 vs 0% of patients receiving best available therapy§ (P <0.0001)1,5

Image that shows COMFORT-I Secondary Endpoint||: 46% of patients receiving Jakafi achieved a ≥50% improvement in Total Symptom Score (TSS) vs 5% of patients receiving placebo (P <0.0001)1,2 Image that shows COMFORT-I Secondary Endpoint||: 46% of patients receiving Jakafi achieved a ≥50% improvement in Total Symptom Score (TSS) vs 5% of patients receiving placebo (P <0.0001)1,2

MEDIAN TIME TO SYMPTOM RESPONSE WAS <4 WEEKS FOR PATIENTS RECEIVING JAKAFI1

Image that shows COMFORT-I Image that shows COMFORT-I

Worsening of TSS is truncated at 150%.1
Derived from Verstovsek S et al. N Engl J Med. 2012;366(9):799-807.

of patients experienced some improvement in symptoms on Jakafi3

Most patients receiving placebo had worsening of symptoms.2

Debilitating Symptoms of MF1,2

  • Abdominal discomfort
  • Early satiety
  • Pain under left ribs
  • Pruritus
  • Night sweats
  • Bone/muscle pain

Jakafi overall survival data

COMFORT-I 5-year overall survival probability data6: Jakafi and placebo

  • At 3 years, survival probability was 70% for patients originally randomized to Jakafi and 61% for those originally randomized to placebo1
  • Overall survival was a prespecified secondary endpoint in COMFORT-I1
Image that shows Overall Survival Kaplan-Meier Curves by Treatment Group in COMFORT-I trial Image that shows Overall Survival Kaplan-Meier Curves by Treatment Group in COMFORT-I trial

Adapted with permission from the Journal of Hematology & Oncology.6

aThe 5-year overall survival analysis is not included in the Full Prescribing Information for Jakafi. Although the 3-year overall survival analysis is presented in the Full Prescribing Information, P values and hazard ratios are omitted from the overall survival Kaplan-Meier curves.3

bCOMFORT-I was not designed to compare survival probabilities between Jakafi and placebo at 3 or 5 years.3

cPatients 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.3

COMFORT-II 5-year overall survival probability data7: Jakafi and best available therapy

  • At 3 years, survival probability was 79% for patients originally randomized to Jakafi and 59% for those originally randomized to best available therapy1
  • Overall survival was a prespecified secondary endpoint in COMFORT-II1
Image that shows Overall Survival Kaplan-Meier Curves by Treatment Group in COMFORT-II Image that shows Overall Survival Kaplan-Meier Curves by Treatment Group in COMFORT-II

Adapted with permission from Leukemia.7
BAT, best available therapy.

aThe 5-year overall survival analysis is not included in the Full Prescribing Information for Jakafi. Although the 3-year overall survival analysis is presented in the Full Prescribing Information, P values and hazard ratios are omitted from the overall survival Kaplan-Meier curves.3

bCOMFORT-II was not designed to compare survival probabilities between Jakafi and best available therapy at 3 or 5 years.3

cPatients randomized to best available therapy 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.3

  Video

Image of Dr Gary Grad

  Video

Image of Dr Gary Grad

Jakafi® (ruxolitinib) in Intermediate-2 or High-Risk Myelofibrosis (MF): Spleen Volume, Symptom, and Overall Survival Data

Hematologist-oncologist Dr Gary Grad reviews data from the COMFORT trials in MF, which included patients with intermediate-2 or high-risk myelofibrosis. Dr Grad begins with a discussion of risk level and corresponding survival in MF. He then discusses results including reduction in spleen volume, symptom reduction (COMFORT-I only), and overall survival probability (which was a secondary endpoint in both trials).

COMFORT, COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment

*COMFORT-I (COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment-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 computed tomography (CT) or magnetic resonance imaging (MRI).1,2

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.3

COMFORT-II (COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment-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.1,5

§Best available therapy 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.3

||A secondary endpoint was the proportion of patients with a ≥50% reduction in TSS from baseline to week 24 as measured by the daily patient diary, the modified Myelofibrosis Symptom Assessment Form. TSS encompasses core symptoms of MF: abdominal discomfort, early satiety, pain under left ribs, pruritus, night sweats, and bone/muscle pain. Symptom scores ranged from 0 to 10, with 0 representing symptoms “absent" and 10 representing symptoms “worst imaginable." These scores were added to create the daily total score, which has a maximum of 60. At baseline, mean TSS was 18.0 in the group receiving Jakafi and 16.5 in the group receiving placebo.1,2

References

  1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
  2. 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.
  3. Data on file. Incyte Corporation. Wilmington, DE.
  4. 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.
  5. 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.
  6. 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.
  7. 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.

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 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 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 2 weeks after the final dose

Please see Full Prescribing Information for Jakafi.