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

Haematologica. 2023 Sep 14. doi: 10.3324/haematol.2021.278613. Online ahead of print.ABSTRACTDiffuse 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 grave 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 characterised by chronically activated B-cell receptor and NFKB signalling along with genetic evidence of immune evasion which may be exploited therapeutically. Improved mechanistic understanding of targ...
Source: Haematologica - Category: Hematology Authors: Source Type: research