Why is regular complete blood count (CBC) with differential monitoring recommended for patients on Vumerity (diroximel fumarate)?

CBC with Differential Monitoring for Patients on Vumerity (Diroximel Fumarate)

Regular CBC with differential monitoring is essential for patients on Vumerity because it helps detect lymphopenia, which can increase the risk of serious opportunistic infections including Progressive Multifocal Leukoencephalopathy (PML).

Rationale for CBC Monitoring

• Vumerity (diroximel fumarate) can cause significant decreases in lymphocyte counts, with mean lymphocyte counts decreasing by approximately 30% during the first year of treatment 1
• In clinical trials, 6% of patients on dimethyl fumarate (which has the same active metabolite as Vumerity) experienced lymphocyte counts <0.5 × 10^9/L compared to <1% of placebo patients 1
• Some patients (2%) experienced prolonged, severe lymphopenia (lymphocyte counts <0.5 × 10^9/L for at least six months) in controlled and uncontrolled clinical trials 1

Recommended Monitoring Schedule

• Obtain a complete blood count (CBC) with differential before initiating treatment with Vumerity 1
• Repeat CBC with differential 6 months after starting treatment 1
• Continue monitoring every 6 to 12 months thereafter 1
• Additional testing should be performed as clinically indicated (e.g., if signs of infection develop) 1

Clinical Significance of Lymphopenia

• Prolonged lymphopenia increases the risk of serious opportunistic infections, including PML 1
• PML is a rare but potentially fatal or severely disabling opportunistic infection of the central nervous system caused by the JC virus 1
• Other serious opportunistic infections have occurred in patients on dimethyl fumarate, including:
  • Viral infections (herpes simplex virus, West Nile virus, cytomegalovirus) 1
  • Fungal infections (Candida and Aspergillus) 1
  • Bacterial infections (Nocardia, Listeria monocytogenes, Mycobacterium tuberculosis) 1

Management of Abnormal Results

• Consider interruption of Vumerity in patients with lymphocyte counts less than 0.5 × 10^9/L persisting for more than six months 1
• Continue monitoring lymphocyte counts until recovery if Vumerity is discontinued or interrupted due to lymphopenia 1
• Consider withholding treatment in patients with serious infections until resolution 1
• Decisions about whether to restart Vumerity should be based on individual clinical circumstances 1

Additional Laboratory Monitoring

• In addition to CBC with differential, liver function tests should be monitored:
  • Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels prior to treatment 1
  • Continue monitoring as clinically indicated 1
  • Discontinue Vumerity if clinically significant drug-induced liver injury is suspected 1

Common Pitfalls and Caveats

• Lymphopenia may persist even after discontinuation of therapy. In patients with prolonged, severe lymphopenia, the median time for lymphocyte counts to return to normal after discontinuing dimethyl fumarate was 96 weeks 1
• Infections can occur in patients with normal lymphocyte counts as well as those with reduced counts, so clinical vigilance is required regardless of laboratory values 1
• Neither Vumerity nor dimethyl fumarate have been studied in patients with pre-existing low lymphocyte counts, so extra caution is warranted in these patients 1

By following this monitoring protocol, clinicians can help minimize the risk of serious complications in patients taking Vumerity while maintaining its therapeutic benefits for multiple sclerosis.