Treating central nervous system lymphoma in the era of precision medicine

ABSTRACT Introduction Primary central nervous system lymphoma (PCNSL) is a rare extra-nodal non-Hodgkin lymphoma that in the vast majority of cases belongs to diffuse large B-cell lymphoma (DLBCL) histology. The standard first-line treatment is based on high-dose methotrexate (HD-MTX) regimens. However, the majority of patients will relapse, leading to a poor prognosis of the disease. Areas covered Reviewed are the potential new therapeutic approaches in PCNSL. With the advent of tailored treatment, immunomodulators and immunotherapies are appearing as new promising therapeutic approaches for this orphan disease. This review seeks to summarize the novel approaches currently under evaluation. Expert opinion The therapeutic management of PCNSL is rapidly evolving with the description of PCNSL molecular alterations. However, due to the rarity of this disease, phase III clinical trials using new therapeutic drugs are still lacking. In addition, the vast majority of newly diagnosed PCNSL affect elderly patients, and specific and adapted clinical trials for this fragile population are warranted. Currently, the use of targeted therapies or immune-mediated treatments is only studied in relapsed/refractory (R/R) PCNSL, but the use of these approaches as a first-line treatment (compared with HD-MTX) could also be used as new promising approaches to decrease the toxicity associated with MTX regimens.