EG04
Dimethyl Fumarate Associated Lymphopenia in Clinical Practice: Implications for Informed Patient Management
Dimethyl fumarate (DMF) has been associated with lymphopenia in clinical trials. This is particularly relevant in light of a recent case of progressive multifocal leukoencephalopathy in a lymphopenic patient on DMF. Lymphopenia occurred in approximately 41% of trial subjects. Lymphocyte counts typically reached nadir at one year and remained stable. DMF was not discontinued in trials solely due to lymphopenia. Patient and clinician conversations at the start of DMF treatment often focus on common side effects and tolerability and may de-emphasize lymphopenia and risk of infection.
Objectives:
1) Describe incidence, time of onset and degree of lymphopenia associated with use of DMF in University of Rochester Multiple Sclerosis Clinic patients.
2) Compare our practical clinical experience with that of the clinical trials to better inform our patients about risk and monitoring on DMF.
Methods:
A retrospective chart review was conducted on all clinic patients who completed DMF enrollment forms between April 2013 and September 2014. Factors reviewed included demographics, DMF duration, blood counts and discontinuation rates. Basic descriptive statistical analyses were completed.
Results:
Of 228 patients prescribed DMF, 152 remained on medication for > 3 months and had at least one follow-up lymphocyte count. Lymphopenia (absolute lymphocyte count (ALC) <0.91 x10^9/L) occurred in 35.5% of our patients during DMF treatment: 3.9% grade 3, 17.1% grade 2 and 14.5% grade 1. ALC primarily remained stable after reaching nadir. Mean duration of DMF treatment when lymphopenia was first identified was 7.5 months. Of the lymphopenic patients, >1/3 developed the lymphopenia within the first 6 months. 7.2% of patients discontinued DMF due to lymphopenia, the majority with ALC<0.6.
Conclusions:
Incidence of lymphopenia described in our clinical practice to date is similar to that described in the clinical trials. It was frequently identified in patients soon after DMF initiation, supporting the practice of monitoring blood counts earlier and educating patients on the importance of follow-up bloodwork. While the risk of opportunistic infections is likely the result of more prolonged lymphopenia, the ALC in DMF does not tend to resolve. Early detection of lymphopenia allows increased time for therapeutic decision-making and more informed risk/benefit discussions with patients.