Dados do Trabalho

Título

Lymphoma associated with Fingolimod treatment: First report of adult-onset case in Brazil

RESUMO

CASE REPORT: A 31-year-old white woman had been suffering from relapsing-remitting multiple sclerosis (RRMS) for more than 8 years. She had been taking fingolimod properly for one and a half years when she developed subacute behavioral changes, dysarthria, right numbness, and hemiparesis. The general laboratory showed 696 lymphocytes. As if she had relapsed, she received intravenous (IV) methylprednisolone with no significant improvement.

Four months later, a repeat MRI scan showed new lesions with gadolinium enhancement in the posterior white matter and brainstem, in addition to meningeal enhancement in the frontal lobe. Fingolimod was discontinued because of possible progressive multifocal leukoencephalopathy. After its discontinuation, two months later, a comprehensive malignancy workup failed, including normal CTs, serous immunofixation and beta-2 microglobulin, a cervical lymph node biopsy, and a brain biopsy with typical MS findings. Subsequent CSF examination revealed 16 cells, and immunophenotyping revealed 3% non-neoplastic clonal plasma cells. Given this atypical evolution, our team of experts concluded a diagnosis of B-cell lymphoma during immunosuppression in advanced RRMS due to immune reconstitution. She received IV rituximab and IV methylprednisolone and had significant improvement.

DISCUSSION: Fingolimod is a sphingosine-1-phosphate (S1P) receptor agonist and the first oral agent approved for the treatment of RRMS. After phosphorylation in vivo, the drug acts as an S1P receptor modulator that binds with high affinity to four of the five known S1P receptors, retaining lymphocytes in lymph nodes and preventing their egress into the peripheral circulation. As a result, the infiltration of autoreactive lymphocytes into the CNS is reduced. It is believed that due to this mechanism, fingolimod may alleviate and reduce the disease burden of lymphoma, increase the efficacy of other treatment options, and improve the function of the immune system in destroying neoplastic cells. Therefore, the drug can be used not only to treat lymphoma, but also to control and prevent disease recurrence in patients in remission.

CONCLUSION: To our knowledge, this is the first report of fingolimod-associated lymphoma confined to the CNS in Brazil. It is a reminder that immunosuppressive drugs have a full spectrum of side effects, not just in infectious diseases. Both solid tumors and hematologic cancers should be considered as possible causes of deterioration.

Palavras Chave

Fingolimod, lymphoma, multiple sclerosis, disease-modifying therapies