Novel agents for primary central nervous system lymphoma (PCNSL): evidence and perspectives

Gerald Illerhaus, Elisabeth Schorb and Benjamin Kasenda


Primary central nervous system lymphoma (PCNSL) is a rare aggressive extranodal Non- Hodgkin Lymphoma. Despite high remission rates can be achieved with high-dose methotrexate based immunochemotherapy, risk of relapse and associated death is still substantial in at least a third of patients. Novel agents for treating lymphoid malignancies have substantially enriched treatment options for PCNSL. We herein systematically review the existing clinical evidence of novel agents in treatment of PCNSL, summarize ongoing studies, and discuss perspectives. The body of evidence for novel agents is still limited to non-comparative studies, however, most promising approaches include bruton-kinase inhibition with ibrutinib and immunomodulatory treatment with e.g. lenalidomide. Targeting the m-TOR pathway seems not being associated with meaningful clinical benefit and evidence of checkpoint inhibition with nivolumab is limited to anecdotal evidence. Future studies should embrace the concept of induction and maintenance therapy as well as the combination of drugs with different mechanisms of action. Selection of patients based on molecular profiling and relapse pattern should be another aspect informing future comparative trials, which are urgently needed to improve prognosis for patients with PCNSL.

  • Submitted January 26, 2018.
  • Accepted July 4, 2018.