Primary central nervous system lymphoma: time for diagnostic biomarkers and biotherapies?

Primary central nervous system lymphoma (PCNSL) is a rare cancer with a somber prognosis in older patients, which it affects predominantly. Only in recent years have molecular alterations characterizing PCNSL been thoroughly described. This opens possibilities for the use of targeted therapies. Developments in imaging and biomarkers have also great potential to help clinicians faced with diagnostic and prognostic uncertainties.

Several biomarkers for PCNSL, such as different microRNAs, which could be tested in cerebrospinal fluid and vitreous fluid, and IL-10, which has been shown to have excellent sensitivity and specificity in the cerebrospinal fluid, have emerged in the last years. Methotrexate-based regimens remain the gold standard first-line treatment, with recent studies looking at the best adjunctive molecules to methotrexate, including rituximab, and at the role of autologous stem cell transplantation. As mutations leading to the activation of nuclear factor-kappa-B signaling are found in most PCNSLs, with mutations of MYD88 and CD79B particularly, ibrutinib is studied as molecule of great interest and encouraging results have been found in pilot studies. There is also great interest in the immunomodulatory drugs (lenalidomide) and immunotherapy (anti-programmed cell death 1/programmed cell death 1 ligand 1).

Identification of molecular genetic and cytokine changes in tumor and liquid biopsies will have an increasing role in the diagnostic and follow-up of PCNSL but also in the treatment and management of the disease.