Understanding Hodgkin Lymphoma Occurrence After Fingolimod Withdrawal

Introduction – Fingolimod, an oral immunomodulator commonly prescribed  for relapsing-remitting multiple sclerosis (MS) treatment, has been associated with lymphoma cases. While it effectively manages MS symptoms, concerns have arisen regarding its association with lymphoma development. Interestingly, some research suggests that fingolimod might exert anticancer effects by reducing the number of tumor-infiltrating lymphocytes. Objective – Describe a patient with MS patient who developed symptoms of Hodgkin’s lymphoma symptoms 11 months after discontinuing fingolimod. Case Report – A 46-year-old female with relapsing-remitting MS since 2007 progressed to secondary progressive MS by 2016. Treated with fingolimod from 2017 to 2022, she discontinued the medication due to persistent lymphopenia. Eleven months post-discontinuation, she presented with cough and dyspnea.  A chest CT scan revealed a mediastinal mass, diagnosed as Hodgkin's lymphoma upon biopsy. Discussion - Fingolimod modulates the Sphingosine-1-Phosphate (S1P) receptor, sequestering lymphocytes in lymphoid tissue. This mechanism underpins its efficacy in MS treatment but also raises concerns about its potential oncogenicity. Chronic fingolimod use has been associated with an increased risk of neoplasms². Although some studies have reported cases of Non-Hodgkin’s Lymphoma linked to Fingolimod in humans⁶⁻⁷, its relationship with Hodgkin’s Lymphoma remains less clear. Notably, Reed-Sternberg cells, the hallmark neoplastic cells in Hodgkin's lymphoma, may express the S1P receptor on their surface¹,³. Exposure to fingolimod could potentially inhibit these cells' migration and proliferation, inducing apoptosis and possibly enhancing the efficacy of chemotherapy³. Final Comments - The 11-month interval between drug discontinuation and symptom onset, along with the diagnosis of Hodgkin’s lymphoma, suggests fingolimod may not have a pro-oncogenic effect on Hodgkin’s lymphoma. Instead, it might suppress Reed-Sternberg cell migration and growth through the mediastinal lymph node chain during treatment.