Disease Modifying Therapies – Risk Management Poster Presentation

P0368 - Persistent severe lymphopenia of at least one-year duration after dimethyl fumarate discontinuation: three case reports (ID 1901)

Speakers
  • N. Gonzalez Caldito
Authors
  • N. Gonzalez Caldito
  • S. O'Leary
  • O. Stuve
Presentation Number
P0368
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Dimethyl fumarate (DMF) is an oral disease-modifying therapy (DMT) that was approved by the FDA to treat relapsing-remitting multiple sclerosis in 2013. Since then, several studies evaluating the safety of this medication have revealed a favorable risk-benefit ratio. The most common adverse events (AEs) are flushing and gastrointestinal symptoms such as nausea or diarrhea. However, there are other less common AE that can potentially be harmful, including persistent lymphopenia. On average, 2.4-7% of the patients on DMF develop grade III lymphopenia (defined as absolute lymphocyte count (ALC) <0.5 × 109 cells/L). In most cases, ALCs reconstitute within weeks to months after discontinuation of DMF.

Objectives

Understanding the AE profile of a medication is important in order to ensure patient safety and provide the most appropriate care.

Methods

Here we report three cases of RRMS presenting with severe persistent lymphopenia of at least one-year duration after DMF discontinuation.

Results

One of the patients continues to have severe lymphopenia 4 years after cessation of DMF. No other anti-proliferative agents were administered to these individuals.

Conclusions

The most important risk factors for developing lymphopenia are increased age, lower baseline ALC, and previous treatment with natalizumab. There are has been a report of 38 cases of severe, prolonged lymphopenia after DMF discontinuation. However, the majority of these patients had grade III lymphopenia persisting for ≥6 months by 3 years on DMF treatment, yet treatment continued for a median of 2.9 years. The unique characteristic of our three patients is that DMF treatment duration was <2 years before grade III lymphopenia onset and despite discontinuation of DMF within 1-year of severe lymphopenia onset, their ALCs didn’t recover. To date, they continue to have severe lymphopenia. This clinical experience highlights the importance of considering lymphopenia as a possible AE prior to starting DMF. Furthermore, it also emphasizes the need to establish protocols to manage DMF induced lymphopenia, especially in situations that require immune-competence for.

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