Dose Optimization Is Key to Maintaining the Balance Between Safety and Efficacy
START: For adults with intermediate- or high-risk myelofibrosis (MF), the recommended starting doses are based on platelet countst1
START: For adults with intermediate- or high-risk myelofibrosis (MF), the recommended starting doses are based on platelet counts1
A complete blood count (CBC) and platelet (PLT) count must be performed before initiating Jakafi.
Jakafi is also available in 10 mg and 25 mg tablets.
Special populations: Please refer to the Full Prescribing Information for starting dose and other dose modifications, and when to avoid treatment in patients with renal or hepatic impairment and in those receiving concomitant strong CYP3A4 inhibitors or fluconazole.
MONITOR: Monitoring patients after initiation of Jakafi is essential, especially during the first 12 weeks of therapy
MONITOR: Monitoring patients after initiation of Jakafi is essential, especially during the first 12 weeks of therapy
A CBC and PLT count must be performed every 2 to 4 weeks until doses are stabilized, and then as clinically indicated. Doses may be titrated based on safety and efficacy.1
...of patients receiving Jakafi in COMFORT-I* required a dose adjustment in the first 12 weeks of therapy2
Monitoring blood counts and using appropriate dose management are essential to achieve desired efficacy and manage cytopenias1
OPTIMIZE: Individualize dosing of Jakafi to optimize the balance between safety and efficacy1
OPTIMIZE: Individualize dosing of Jakafi to optimize the balance between safety and efficacy1
Managing anemia and thrombocytopenia
- In COMFORT-I, grades 3 and 4 thrombocytopenia or anemia occurred in 13% and 45% of
patients receiving Jakafi, respectively. All grades of thrombocytopenia or anemia occurred in
70% and 96% of patients receiving Jakafi, respectively1,3 - Dose modifications, temporarily withholding Jakafi, and/or transfusions may be required for patients developing anemia or thrombocytopenia1
- Interrupt treatment for bleeding, neutropenia (absolute neutrophil count [ANC] <0.5 × 109/L), or thrombocytopenia (based on starting platelet count)1
<1% of patients receiving Jakafi in the COMFORT*† studies discontinued due to anemia or thrombocytopenia1
Dosing in COMFORT-I
- Treatment with Jakafi can cause thrombocytopenia, anemia and neutropenia, which are each dose-related effects. Perform a pre-treatment 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 (absolute neutrophil count [ANC] <0.5 × 109/L) was generally reversible by withholding Jakafi until recovery
Dose may be increased in the case of an insufficient response1
Efficacy based on titrated dose
Graphic adapted with permission from Haematologica.
- Doses may be increased if the response is insufficient and platelet, hemoglobin, and neutrophil counts are adequate, and treatment has not been reduced or interrupted in the prior 4 weeks.1 (See next section, Appropriate Dose Management, for criteria for increasing dose)
- Doses should not be increased during the first 4 weeks of therapy and not more frequently than every 2 weeks1
- Discontinue Jakafi if there is no spleen size reduction or symptom improvement after 6 months of therapy1
- In patients with starting platelet counts ≥100 × 109/L, based on limited clinical data, long-term maintenance at a 5 mg twice daily dose has not shown responses. Continued use at this dose should be limited to patients in whom the benefits outweigh the potential risks1
Appropriate dose management
Dose Modifications for Patients With Starting PLT Count ≥100 × 109/L
Dose Modifications for Patients With Starting PLT Count 50 to <100 × 109/L
Dose modification for bleeding
Interrupt treatment for bleeding requiring intervention regardless of current PLT count. Once the bleeding event has resolved, consider resuming treatment at the prior dose if the underlying cause of bleeding has been controlled. If the bleeding event has resolved but the underlying cause persists, consider resuming treatment with Jakafi at a lower dose.
Special populations
Dose modifications in patients with renal or hepatic impairment, or when coadministered with strong CYP3A4 inhibitors or fluconazole
For further information and to download the Jakafi dosing guide, click here.
*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 myelofibrosis. 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). A secondary endpoint was the proportion of patients with a ≥50% reduction in Total Symptom Score from baseline to week 24 as measured by the daily patient diary, the modified Myelofibrosis Symptom Assessment Form. 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).1,3
†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 myelofibrosis. 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
References
- Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
- Verstovsek S, Mesa RA, Gotlib J, et al. Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I. Haematologica. 2013;98(12):1865-1871.
- 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.
- 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.
