Primary central nervous system lymphoma: Evolving treatment strategies to achieve improved long-term disease control

Abstract

Objective

Despite high initial response rates to chemotherapy, long-term disease control in primary central nervous system lymphoma (PCNSL) remains challenging, with high relapse rates and no universally accepted standard for induction or consolidation therapy. This review discusses current strategies, new advancements and clinical trial results for PCNSL.

Data Sources

An extensive Medline, Embase and Cochrane search of peer-reviewed sources reporting on pharmacotherapy of PCNSL was performed (1/1/2000-12/31/2025). Analysis of original research including clinical trial results, retrospective series and other reports were included in this review.

Data Summary

This review summarizes the current understanding of PCNSL, including epidemiology, clinical presentation, diagnostic evaluation, and response assessment, with a focus on pharmacologic management. We discuss modern induction strategies centered on high-dose methotrexate (HD-MTX) and rituximab, consolidation approaches including reduced-dose whole-brain radiotherapy (WBRT), autologous stem cell transplantation (ASCT), and maintenance strategies, as well as emerging therapies for relapsed or refractory disease. A case of a 76-year-old patient achieving sustained remission exceeding seven years following rituximab plus HD-MTX induction and consolidative therapy is presented to illustrate the potential for durable disease control and even cure. These data underscore the importance of individualized treatment selection based on patient age, fitness level and response to induction and highlight that lasting remission is achievable in select patients with optimized, multimodal therapy.

Conclusions

Despite its rarity, PCNSL remains a therapeutically challenging malignancy. HD-MTX–based chemotherapy remains the cornerstone of first-line treatment, and the addition of rituximab has been associated with more sustained responses. Although relapses are not uncommon, long-term remission is achievable. Clinical trials of newer agents, alone or added to a backbone of traditional chemotherapy, are warranted in the 1^st and subsequent lines of therapy. Continued prospective research and international collaboration are essential to integrate precision oncology to the bedside of patients with PCNSL.