What are the management recommendations for patients developing leukocytosis while being treated with Ocrevus (ocrelizumab)?

Management of Leukocytosis in Patients Treated with Ocrevus (Ocrelizumab)

For patients developing leukocytosis while on ocrelizumab treatment, the increase in white blood cell count should be interpreted as a potential treatment-related effect that typically does not require discontinuation of therapy unless severe complications develop.

Understanding Leukocytosis in Ocrelizumab Treatment

• Leukocytosis (elevated white blood cell count) can occur as a treatment effect in patients receiving ocrelizumab, similar to what is observed with other disease-modifying therapies 1
• An increase in white blood cell count should not automatically lead to reclassification of disease status or unnecessary treatment interruption 2
• The mechanism is likely related to the immunomodulatory effects of ocrelizumab as an anti-CD20 monoclonal antibody that depletes B cells 3

Assessment of Leukocytosis

Initial Evaluation:

• Determine severity of leukocytosis (specific WBC count) 4
• Assess for signs and symptoms of infection which may require separate management 1
• Evaluate for other potential causes of leukocytosis (infection, inflammation, stress response) 5
• Monitor for complications of severe leukocytosis such as:
  • Leukostasis (particularly with WBC >100,000/μL) 4
  • Tumor lysis syndrome 4
  • Disseminated intravascular coagulation (DIC) 4

Management Algorithm

For Mild to Moderate Asymptomatic Leukocytosis:

1. Continue ocrelizumab therapy with regular monitoring 1
2. Monitor complete blood count at more frequent intervals (e.g., monthly) until stabilized 2
3. No specific intervention required if the patient is asymptomatic 1

For Significant Leukocytosis (WBC >30,000/μL) or Symptomatic Patients:

1. Consider cytoreductive therapy with hydroxyurea (2-4g per day) if symptoms of leukostasis develop 2
2. For extreme leukocytosis with symptoms, treatment options include:
   • Hydroxyurea as first-line cytoreductive agent 2
   • Consider short course of corticosteroids (prednisone 20 mg/day for 3 days) if significant symptoms are present 2

For Severe Leukocytosis with Complications:

1. Temporarily withhold ocrelizumab until leukocytosis resolves 6
2. Implement cytoreductive measures with hydroxyurea 2
3. Consider hospitalization for patients with:
   • Signs of leukostasis (neurological symptoms, respiratory distress)
   • Very high WBC counts (>100,000/μL)
   • Evidence of organ dysfunction 4

Special Considerations

• Patients with comorbidities are at higher risk for complications and require closer monitoring 1
• Avoid leukapheresis unless absolutely necessary due to risk of complications 2
• Most cases of treatment-related leukocytosis will resolve without specific intervention 1
• Prophylactic corticosteroids may be considered in patients with history of significant leukocytosis with previous ocrelizumab doses 2

Follow-up Recommendations

• Monitor complete blood count before each ocrelizumab infusion 6
• For patients with history of leukocytosis, consider more frequent monitoring between doses 2
• Evaluate for signs of infection at each visit, as ocrelizumab-treated patients have increased infection risk 1
• Continue long-term monitoring of immunoglobulin levels, as abnormal IgM levels may contribute to infection risk 1

Common Pitfalls to Avoid

• Do not automatically discontinue ocrelizumab due to mild-moderate leukocytosis without other symptoms 2
• Avoid misinterpreting treatment-related leukocytosis as disease progression 2
• Do not initiate aggressive cytoreductive therapy for asymptomatic mild-moderate leukocytosis 2
• Remember that time on ocrelizumab treatment is not significantly associated with increased serious infection risk 1