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Diffuse large B-cell lymphoma involving the central nervous system: biologic rationale for targeted therapy.

Published version
Peer-reviewed

Repository DOI


Type

Article

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Authors

Roschewski, Mark 
Hodson, Daniel J 

Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma curable even in advanced stages. DLBCL involving the central nervous system (CNS) is more difficult to cure and fewer treatment options exist. Primary CNS lymphoma (PCNSL) refers to aggressive lymphomas confined to the CNS, and are almost always DLBCL. Standard approaches for PCNSL use high-dose methotrexate-based combinations as induction therapy and younger patients often receive dose-intensive consolidation. However, dose-intensive therapies are not suitable for all patients, and older patients have fewer effective treatment options. Patients with relapsed or chemotherapy-refractory disease have a very poor prognosis. Secondary CNS lymphoma (SCNSL) describes aggressive lymphomas involving the CNS at initial presentation or relapses within the CNS after treatment for systemic DLBCL. Isolated CNS relapse is often managed as PCNSL, but patients with synchronous involvement of DLBCL in both the periphery and the CNS pose a unique clinical challenge. Insights into the molecular circuitry of DLBCL have identified distinct genetic subtypes including cases with a predilection for CNS invasion. PCNSL and subsets of SCNSL are characterized by chronically activated B-cell receptor and NFκB signaling along with genetic evidence of immune evasion which may be exploited therapeutically. Improved mechanistic understanding of targetable pathways underpinning CNS lymphomas has led to numerous clinical trials testing targeted agent combinations and immunotherapy approaches with promising early results. Biologically rational strategies may further improve the cure rate of CNS lymphomas, either by overcoming intrinsic or acquired treatment resistance and/or by being broadly applicable to patients of all ages.

Description

Keywords

Humans, Neoplasm Recurrence, Local, Lymphoma, Large B-Cell, Diffuse, Central Nervous System Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Central Nervous System, Biological Products

Journal Title

Haematologica

Conference Name

Journal ISSN

0390-6078
1592-8721

Volume Title

Publisher

Ferrata Storti Foundation (Haematologica)
Sponsorship
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (203151/A/16/Z)
Medical Research Council (MC_PC_17230)

Version History

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2*
2024-02-15 16:31:05
Published version added
2023-12-19 00:30:46
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