Have treatment protocols for primary CNS lymphoma advanced in the past 10 years?

ABSTRACT

Introduction: Primary CNS lymphomas (PCNSL) are highly aggressive tumors and optimal treatment is not yet defined. For the last two decades, clinical trials have focused on developing efficient chemotherapy protocols with or without dose-reduced radiation to avoid late cognitive decline after whole brain radiotherapy (WBRT).

Areas covered: This review addresses the question if these substantial developments have led to clinically relevant therapeutic improvement for PCNSL within the last decade.

Expert opinion: The high risk of neurotoxic side effects of WBRT was further substantiated, and in most centers WBRT is omitted from first-line treatment in patients eligible for high-dose systemic methotrexate (HDMTX)-based chemotherapy. Intensified polychemotherapy regimens, particularly high-dose chemotherapy regimens with autologous stem cell transplantation (HD-ASCT), were investigated within prospective multicenter randomized trials and have achieved long-term disease control in a fraction of patients, but no significant progress was made for elderly patients, who are not able to tolerate intensified chemotherapy. Results on the efficacy of rituximab in PCNSL are conflicting; it did not show clinical benefit in a recent large prospective multicenter randomized trial. New substances such as immune-checkpoint inhibitors and targeted molecules are subject to investigation, but have not yet been implemented in clinical routine.

KEYWORDS:

• PCNSL
• methotrexate
• rituximab
• HD-ASCT
• consolidation therapy

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Article highlights

• Whole brain radiotherapy should be omitted from first-line treatment for patients able to receive HDMTX-based chemotherapy

• Significant therapeutic progress has been made for younger patients able to receive intensified chemotherapy protocols

• For elderly patients, no relevant progress in treatment of PCNSL has been achieved

• No long-term effective treatment option apart from HD-ASCT exists for relapsed or refractory PCNSL

• Novel agents hold promise but have not found their way into everyday practice

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

Uwe Schlegel has received honoraria as a speaker from Novartis, GSK, medac and as an Advisory Board member from Roche and Optune. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The paper received no funding.