Advances in therapeutic strategies for primary CNS B-cell lymphomas

Introduction Primary CNS lymphoma (PCNSL) has traditionally been treated with induction HD-MTX-based chemotherapy, followed by consolidation whole-brain radiotherapy. However, this approach is associated with significant neurocognitive complications, especially in older patients. Therefore, different consolidation protocols have been evaluated. High-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) has the best long-term survival outcomes in younger patients.Areas covered In this review of the literature, we focus on the overall therapeutic strategy and advances in the management of the aggressive primary CNS B-cell lymphomas.Expert opinion In young and fit PCNSL patients, HD-ASCT is the preferred consolidation strategy to achieve long-term survivals. Older patients with good performance status should also be evaluated for MTX-based induction polychemotherapy followed by ASCT. However, management of PCNSL patients remains challenging, and new avenues with targeted therapies are under investigation. To date, ibrutinib, lenalidomide, and immune checkpoint inhibitors appearto be promising in PCNSL. However, as monotherapy, durable responses are less likely to be achieved. Unfortunately, when combined with chemoimmunotherapy, considerable toxicity and mortality have been reported. Clinical trials on these molecules are aiming to reduce toxicity and maintain responses. CAR-T-cell therapy has recently emerged as a further option. It has shown efficacy in patients with secondary CNS lymphoma, with few but encouraging results in primary CNSL.