SOHO State of the Art Updates and Next Questions | Management of Primary Central Nervous System Lymphoma

Primary Central Nervous System Lymphoma (PCNSL) is a rare and aggressive form of extranodal non-Hodgkin lymphoma. Recent insights into the molecular characteristics of neoplastic B-cells are opening the era of precision diagnostics with the development of liquid biopsy based on biomarkers, such as interleukin-10 level and the presence of MYD88^L265P mutation, in the cerebrospinal fluid. Moreover, artificial intelligence (AI) tools are being developed to enhance our capacity to extract information from magnetic resonance images. Therapeutic advancements over the last decade have achieved curative outcomes in almost half of the patients eligible for intensive treatment. For fit patients, the current gold standard remains intensive induction with high-dose methotrexate (HD-MTX)-based polychemotherapy followed by thiotepa-conditioned autologous stem cell transplantation (ASCT). In the elderly, stratification according to HD-MTX suitability is mandatory. Moreover, in this population, age-adjusted consolidation with ASCT can represent a valid option, achieving remarkable outcomes while mitigating treatment-related toxicity. Whole-brain radiotherapy (WBRT) can be considered an alternative strategy when ASCT is not feasible. The management of relapsed/refractory disease is being transformed by the integration of Bruton's tyrosine kinase inhibitors and immunomodulatory drugs, which offer promising efficacy, particularly within synergistic, multitargeted combinations. Furthermore, evidence from international registries has shown promising activity of chimeric antigen receptor T (CAR-T) in relapsed/refractory patients, with acceptable toxicity. Looking ahead, the translation of circulating tumor DNA profiling "from bench to bedside" for measurable residual disease monitoring, alongside the integration of AI in radiomic assessment, and the introduction of personalized targeted approaches will further revolutionize the management of Primary Central Nervous System Lymphoma.