Tumefactive multiple sclerosis lesions associated with fingolimod treatment: Report of 5 cases

Background and objective: Fingolimod is a sphingosine 1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes and prevents them from entering the central nervous system. There have been increasing reports of severe rebounds with tumefactive demyelinatinglesions (TDLs) in patients with multiple sclerosis under fingolimod treatment, as well as following therapy discontinuation. Our objective is to review the clinico-radiological characteristics of patients with TDLs associated with fingolimod. Methods: Retrospective review of medical records of MS patients from our center, who were treated with fingolimod and developed TDLs. We review the literature. Results: We found 5 cases: 4 developed TDLs as rebounds after treatment cessation and 1 under treatment. The 4 rebound cases were women, with a mean age of 34.7 years (SD = 3.6) and a mean disease duration of 10.2 years (SD = 4.1). The mean duration of fingolimod treatment before discontinuation was 36.2 months (SD = 22.4) and the mean time lapse between treatment withdrawal and rebound was 9.75 weeks (SD = 7.4). The total pre-rebound lymphocyte count (cells/mm3) was 482.5 (SD = 325.7) and1017.5 (SD = 364.8) during rebound. The TDL patient under fingolimod was a 36-year-old man who had been on fingolimod for 32 months after switching from glatiramer acetate. TDLs were multiple in 2 cases and solitary in 3. Acute treatment for rebound included high dose steroids (5/5), plasma exchange (3/5) and rituximab (2/5). Treatment after fingolimod included rituximab (2/5), alemtuzumab (2/5) and glatiramer acetate (1/5). Conclusions: Our study, along with similar reports in literature, highlights the need for close monitoring in patients who plan to switch from fingolimod to other treatments because of the risk of severe rebound. The etiopathogenic association between fingolimod and TDLs is not clear, but given the increasing reports of cases it should be taken into account for treatment selection in patients with this type of lesions.