Dimethyl Fumarate Associated Lymphopenia Appears Driven by Selective CD8+ T Cell Depletion

Thursday, June 2, 2016
Exhibit Hall
Jong-Mi Lee, MSN - NP , Neuroscience, Stanford Healthcare, Stanford, CA
Jeffrey Dunn, MD , Neurology & Neurological Sciences, Stanford University Medical Center, Stanford, CA
Jong-Mi Lee, MSN - NP , Neuroscience, Stanford Healthcare, Stanford, CA

Background: Tecfidera, an oral treatment option for multiple sclerosis (MS), is associated with lymphopenia as demonstrated in CONFIRM/DEFINE

Objectives: To evaluate the behavior of T cells in the lymphocyte subset who experience dimethyl fumarate (DMF)- induced lymphopenia.

Methods: A retrospective chart review was conducted of 13 patients with MS treated with DMF. Data was analyzed on patients with an absolute lymphocyte count that demonstrated at least a 30% drop from their baseline prior to starting DMF who underwent flow cytometry lymphocyte subset analysis after being on DMF treatment for at least 3 months.

Results: The population demographics included 11 female patients (85%) and 2 male patients (15%): with a mean age of 54.4 + 0.7 years, disease duration of 9.2 + 0.6 years. With the exception of one patient, all 12 patients demonstrated a drop in T cells. The CD8+ lymphocytes showed a greater reduction in % lower limit of normal (LLN) relative to CD4+ lymphocytes. CD19+ B cells were reduced in 5 patients. One patient discontinued DMF after 18 months due to a new relapse and gadolinium-enhancing lesions on magnetic resonance imaging. One patient discontinued DMF treatment after 24 months due to persistent Grade 3 lymphopenia.

Conclusions: Previous studies have been performed to understand whether primarily T cells or B cells drive lymphopenia. Performing routine flow cytometry may help manage patient response and safety to DMF treatment.