Primary CNS lymphoma commonly expresses immune response biomarkers

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Primary central nervous system lymphoma (PCNSL) is a rare malignancy with limited genomic and immunological data.
• Previous observations suggest potential efficacy of immune checkpoint inhibitors (ICIs) in PCNSL patients.

Purpose of the Study:

• To genetically characterize PCNSL and determine the potential benefit of ICIs for a majority of patients.
• To profile mutations, gene amplifications, fusions, and PD-1/PD-L1 expression in PCNSL.

Main Methods:

• Next-generation sequencing (NGS) for mutations, amplifications, and microsatellite instability (MSI).
• RNA sequencing for gene fusions.
• Immunohistochemistry for PD-1 and PD-L1 expression; Tumor Mutational Burden (TMB) calculation.

Main Results:

• High PD-L1 expression observed in 37.5% of patients; PD-1 expression in 85.7% of tumors.
• Tumor Mutational Burden (TMB) ≥5 mt/Mb in 90.5% of tumors, with 19% having high TMB (≥17 mt/Mb).
• Frequent mutations in MYD88 (81%), CD79B (55%), and PIM1 (55%); no MSI detected; ETV6-IGH fusion identified in one case.

Conclusions:

• High TMB and PD-L1 expression in a significant proportion of PCNSL patients suggest potential for ICI therapy.
• Over 90% of PCNSL patients may be candidates for immune checkpoint inhibitor treatment based on TMB biomarker.