[Primary central nervous system lymphoma following immunotherapy for metastatic melanoma]

Anti-PD-1 and anti-CTLA-4 monoclonal antibodies are used in melanoma, while anti-PD-1 are also used in Hodgkin's lymphoma. Primary central nervous system lymphoma is a rare form of non-Hodgkin's lymphoma with few effective treatments. However, several recent studies have reported multiple cases of non-Hodgkin's lymphoma and primary central nervous system lymphoma treated by anti-PD-1 antibodies with favourable responses.

This study focuses on the case of a 59-year-old man with metastatic melanoma treated by immunotherapy (anti-CTLA-4 followed by anti-PD-1). He underwent 28 courses of therapy with pembrolizumab. Treatment was stopped after clinical and radiological remission. The patient presented left hemiparesis and a primary central nervous system lymphoma was diagnosed two months after discontinuation of immunotherapy. He started urgent high-dose methotrexate chemotherapy but without significant results. Despite second-line chemotherapy with R-ICE (rituximab-ifosfamide, carboplatin and etoposide), the patient died.

Several hypotheses may be advanced regarding a possible relationship between immunotherapy and the occurrence of this primary central nervous system lymphoma. The lymphoma may have been pre-existing and controlled by immunotherapy, but progressing rapidly after treatment, or it may have been induced by the immunotherapy. However, immunotherapy may have played no role; the relationship between melanoma and lymphoma is well known.

While immunotherapy cannot be unequivocally incriminated in primary central nervous system lymphoma, this case raises many questions about the imputability of immunotherapy in the occurrence of secondary cancers, including lymphomas.