Management of lymphopenia associated with dimethyl fumarate and fingolimod

Aim

To improve variances in treatment decisions by:

• reviewing the number of people with relapsing remitting MS on dimethyl fumarate (DMF) or fingolimod (FTY) referred to the hospital’s pharmacist-led off-protocol blood monitoring clinic due to lymphopenia
• reviewing lymphopenia treatment options and outcomes for these patients
• reviewing the outcomes of lymphopenia patients who switched DMTs

Headlines

• People taking DMF or FTY may develop severe, prolonged lymphopenia. This can increase the risk of infections, including progressive multifocal leukoencephalopathy (PML)
• The UK SMC recommends DMF treatment be stopped if lymphocyte counts (LC) remain <0.5×10⁹/l for more than six months
• For FTY, an absolute LC of <0.2×10⁹/l should lead to “treatment interruption until recovery”, according to the UK SMC
• The National Hospital for Neurology and Neurosurgery has no agreed guidelines for the long-term management of these patients. This may lead to variances in treatment decisions when lymphopenia occurs

Key findings

• Between December 2019 and January 2019, LC of <0.5×10⁹/L were seen in 27 of 478 DMF patients (6%); 16 of 179 FTY patients (18%) reached a minimal LC <0.2×10⁹/L on at least one occasion
• DMF: Patients with lymphopenia were more likely to continue with DMF than stop despite LC of <0.5×109/L for more than six months
• FTY: Patients with lymphopenia were more likely to continue treatment than stop, due to the risk of rebound relapse
• Patients who continued on standard or low doses of DMF or FTY despite low LC saw no recovery and experienced prolonged lymphopenia
• 20 patients (DMF n= 4, FTY n=16) were referred for LC monitoring during a washout period prior to starting an alternative DMT
• For those who switched treatment, wash out periods were varied. There was no correlation between lymphopenia grade and length of time to LC recovery

Recommendations

Early interventions, such as switching to an alternative DMT or treatment cessation, are needed to avoid prolonged lymphopenia in MS patients on DMF or FTY.

More real-world data is needed to establish trends and guide timelines for DMT switching in these patients.