Absolute Lymphocyte Count Before Initiating Dimethyl Fumarate
Yes, an absolute lymphocyte count (ALC) should be obtained before initiating dimethyl fumarate therapy to establish a baseline and identify patients who may be at risk for developing severe lymphopenia. 1
Rationale and Recommendations
- The FDA drug label explicitly states: "Obtain a complete blood cell count (CBC) including lymphocyte count before initiation of therapy" with dimethyl fumarate 1
- Dimethyl fumarate causes a reduction in lymphocyte counts as an expected pharmacodynamic effect, with mean reductions of approximately 30-45% during the first year of treatment 1, 2
- Baseline ALC values are important for comparison to detect significant drops during treatment and to identify patients who may be at higher risk for developing severe lymphopenia 2
Monitoring Protocol
- Obtain CBC with lymphocyte count before starting dimethyl fumarate 1
- Repeat CBC at 6 months after starting treatment 1
- Continue monitoring every 6-12 months thereafter, and as clinically indicated 1
- Consider more frequent monitoring in high-risk patients (age >55, lower baseline ALC, recent natalizumab exposure) 3
Clinical Significance of Lymphopenia
- Severe, prolonged lymphopenia (ALC <0.5 × 10⁹/L for ≥6 months) occurs in approximately 2% of patients and is associated with increased risk of opportunistic infections 1, 4
- Progressive multifocal leukoencephalopathy (PML) has occurred in patients with prolonged lymphopenia while on dimethyl fumarate 1
- Other serious opportunistic infections (herpes simplex, cytomegalovirus, fungal, and bacterial) have been reported in patients with reduced ALC 1
Management of Lymphopenia
- Consider interruption of dimethyl fumarate in patients with lymphocyte counts <0.5 × 10⁹/L persisting for more than six months 1
- The EU summary of product characteristics recommends discontinuing treatment when ALC is <0.2 × 10⁹/L 5
- After discontinuation, lymphocyte counts typically begin to recover within 4-8 weeks but may take longer to return to normal levels 1, 2
- In rare cases, severe lymphopenia may persist for years after discontinuation 6
Risk Factors for Developing Lymphopenia
Practical Considerations
- Early drops in ALC have been associated with the development of severe prolonged lymphopenia 2
- A significant association has been found between decreased lymphocyte counts over the first 6 months of treatment and the development of severe lymphopenia by the end of the study period 7
- Monitoring ALC is an effective strategy to identify patients at risk for developing severe, prolonged lymphopenia 2, 4
By obtaining a baseline ALC before initiating dimethyl fumarate and following the recommended monitoring schedule, clinicians can identify patients at risk for developing severe lymphopenia and make appropriate treatment decisions to minimize the risk of serious infections.