Following the occurrence of 1 case of progressive multifocal leukoencephalopathy (PML) the DMF label was amended in 2015 to recommend treatment interruption for patients with severe, prolonged lymphopenia.

Examine the clinical implications of DMF-associated lymphopenia and post-treatment ALC dynamics in pts with RRMS.

An integrated analysis of the DMF Phase 2b, Phase 3 (DEFINE/CONFIRM) and extension (ENDORSE) studies was conducted. Data from 1st DMF exposure were analysed. ALCs were assessed at weeks (weeks) 4, 8, 12, and every 12 weeks thereafter.

As of 01 Sept 2017, the analysis population comprised 2513 pts (10454 patient-years). In pts followed for up to 11 yrs, severe, prolonged lymphopenia was not associated with increased incidence of serious infection (0.016 vs. 0.010 for patients with ALC always above normal) or serious herpes zoster (0 vs. 0.006 for patients with ALC always above normal). One fatal case of PML previously occurred in the setting of severe lymphopenia of ∼3.5 years duration.

Following the implementation of a stopping rule requiring patients with an ALC<0.5×109/L for≥6 months to discontinue DMF treatment, no additional cases of PML have been observed in this study. In patients with mild or moderate lymphopenia [ALC<0.91×10^9/L; N=138] while on DMF, and with an ALC<0.91×109/L at DMF discontinuation, median time to ALC≥0.8×10^9/L was 6 weeks post-DMF discontinuation.

These data support that DMF-associated lymphopenia is not associated with increased incidence of serious/opportunistic infection aside from very rare PML. For the majority of pts, ALCs increased following DMF discontinuation within 2 months.