What is the typical dosing of ruxolitinib (Jakafi) for polycythemia vera (PCV)?

Ruxolitinib Dosing in Polycythemia Vera

For polycythemia vera (PV), ruxolitinib should be initiated at 10 mg orally twice daily, with dose adjustments based on platelet counts and clinical response. 1

Initial Dosing Strategy

The starting dose of ruxolitinib in PV is 10 mg twice daily for most patients, regardless of platelet count, which differs from the platelet-based dosing used in myelofibrosis. 1, 2 This standardized approach was validated in the pivotal RESPONSE trials and is now the FDA-approved dosing regimen for PV. 3, 4, 2

Key distinction: While NCCN guidelines describe platelet-stratified dosing for myelofibrosis (5-20 mg twice daily based on platelet counts), this does NOT apply to PV treatment. 1 The evidence from RESPONSE and RESPONSE-2 trials consistently used 10 mg twice daily as the starting dose for PV patients. 3, 4, 2

Dose Escalation Protocol

After 3 months of treatment, the dose may be increased if hematocrit control is not achieved. 5 The European LeukemiaNet guidelines support dose adjustments at 4-week intervals in 5 mg twice daily increments, though specific maximum doses for PV are not as clearly defined as in myelofibrosis. 1

• Dose increases should not occur during the first 4 weeks of therapy 1
• Increases should not be more frequent than every 2 weeks 1
• The goal is achieving hematocrit <45% without phlebotomy 5, 2

Monitoring Requirements

Complete blood count and comprehensive metabolic panel with uric acid and LDH must be performed before initiating therapy, every 2-4 weeks until doses are stabilized, and then as clinically indicated. 1 This intensive monitoring is critical because:

• Thrombocytopenia and anemia are the most common hematologic adverse events 1, 4
• Dose reductions or interruptions may be necessary based on blood counts 1, 6
• Lipid parameters should be assessed as ruxolitinib increases total cholesterol, LDL, and triglycerides 1, 6

Clinical Context for Use

Ruxolitinib is indicated as second-line therapy for PV patients who are resistant to or intolerant of hydroxyurea. 1 The European LeukemiaNet provides a strong recommendation for ruxolitinib in this setting, though they note the confidence in outcome measures is moderate. 1

Both interferon and ruxolitinib are appropriate second-line options, with the choice based on patient age and drug availability—interferon should be preferred in young patients requiring long-term treatment. 1 This reflects concerns about long-term safety data with ruxolitinib in younger populations.

Efficacy Outcomes

In the RESPONSE-2 trial of PV patients without splenomegaly, 62% achieved hematocrit control at week 28 with ruxolitinib versus 19% with best available therapy. 2 Long-term follow-up demonstrated:

• At 5 years, 74% probability of maintaining primary composite response 4
• Median time to hematocrit control was 2.2 months 5
• 93.8% of first-line and 88.2% of second-line patients achieved hematocrit control 5

Critical Safety Considerations

Ruxolitinib should never be discontinued abruptly—tapering is essential when stopping therapy to avoid withdrawal syndrome. 1, 6 Sudden discontinuation can cause a shock-like syndrome due to reactivation of inflammatory cytokines. 6

Common adverse events requiring dose modification include:

• Anemia (most frequent, usually grade 1-2) 4, 7
• Thrombocytopenia (managed with dose reduction or interruption) 1, 6
• Increased infection risk, including herpes zoster and opportunistic infections 6

Tuberculosis screening is mandatory before initiating treatment, and hepatitis B/C testing should be performed to prevent viral reactivation. 8, 6

Dose Modifications for Toxicity

Thrombocytopenia should be managed by dose reduction or interruption at the discretion of the treating clinician based on clinical parameters. 1 Platelet transfusions may be necessary. 1 Management of anemia may require blood transfusions and/or dose modifications. 1 Severe neutropenia (ANC <0.5 × 10⁹/L) was generally reversible by withholding ruxolitinib. 1

Special Populations

Dose adjustments are required for patients with renal or hepatic impairment. 6 The NCCN guidelines note that certain clinical situations may support initiation at a lower dose with subsequent adjustments, though specific recommendations are not detailed. 1