Role of targeted therapy in central nervous system lymphoma

Abstract

Longer life expectancy, better diagnostic measures and advances in neuro-imaging account for the increasing numbers of diagnosed cases of primary central nervous system (CNS) lymphoma (PCNSL). Unfortunately, PCNSL is usually diagnosed late and that leads to poor performance status of patients, reducing their chances of accurate and timely therapy. This accounts for significant differences between real-life treatment outcomes and clinical trials. Although PCNSL had long been considered incurable, rapidly evolving therapeutic paradigms have shown significant progress with an absolute necessity for efficient diagnosis, staging and initiation of therapy conducted at experienced centers. High-dose methotrexate combined with rituximab and high-dose cytarabine in younger patients, or alkylating agents and rituximab in older patients, still remains the standard of care as induction therapy, while relapsed/refractory disease is a challenge necessitating the search for new, safe and effective therapeutic approaches.

Thanks to the discovery of the crucial molecular pathways leading to lymphomagenesis, it is now possible to target points of deregulation of specific pathways and stop the cancerous process. The very recent developments of efficient therapies, including high-dose methotrexate-based chemotherapy and targeted therapies comprising the monoclonal antibody rituximab and the immune checkpoint inhibitors lenalidomide and ibrutinib, have brought about improved outcomes.

Such novel agents bring hope for better results and seem to hold great promise for the treatment of patients with relapsed/refractory PCNSL. The key to future approaches is to target different molecular pathways in order to overcome mechanisms of resistance.