Work

Rare-22. Frequent High Tumor Mutational Burden (tmb) and Pd-l1 Expression in Primary Cns Lymphoma (pcnsl)

Year: 2018

Type: article

Abstract: PD-1 and PD-L1 expression has not been well-described in PCNSL. In one report of 20 PCNSL tumors, PD-1 and PD-L1 expression on tumor cells (TC), tumor-infiltrating lymphocytes (TIL), or tumor-associated macrophages (TAM) was seen in 90% (Clin Neuropathol 2014;PMID:24359606). Another report of 4 patients with relapsed PCNSL showed clinical and radiographic responses to PD-1 blockade (Blood 2017;PMID:28356247). Samples from 36 subjects with large B-cell PCNSL submitted to Caris Life Sciences from 20132018 were tested by NextGen Sequencing (NGS, 592-gene panel [n=30] or 45-gene panel [n=6]) for mutations and gene amplification. RNA sequencing (Archer FusionPlex) was used to detect gene fusions. TMB was calculated using somatic nonsynonymous missense mutation, and microsatellite instability (MSI) was tested by NGS. PD-L1 IHC (SP142) was tested on tumor cells and PD-1 was determined on TIL. High PD-L1 expression (>5% staining) was seen in 14 cases (39%), and low expression (15% staining) was noted in 11 cases (31%). Another 11 cases (30%) showed absent PD-L1 expression. PD-1 expression (>1 cell/high-power field) was seen in 10/12 tumors (83%) without correlation with PD-L1. TMB of 5 mutations per megabase (mt/MB) was seen in all 30 tumors tested with the 592-gene panel, with 27% (n=8) exhibiting high TMB (17 mt/MB). No samples had high level MSI. Overall, 18/30 tumors (60%) had high PD-L1 or high TMB. Mutations in 25 genes were seen; the most frequent were MYD88 (26/30, 87%, all L265P), PIM1 (16/30, 60%), and CD79B (15/30, 50%, all Y196). Among 7 cases tested with RNA-sequencing, one recently reported ETV6-IGH fusion was found (Neuro-Oncology 2018;PMID:29432597). CONCLUSIONS: We found high TMB and PD-L1 expression in PCNSL with no correlation. Nearly two thirds of PCNSL tumors harbor favorable biomarker profiles with anticipated responsiveness to checkpoint inhibitors. Further studies are needed to validate initial results.

Source: Neuro-Oncology

DOI: 10.1093/neuonc/noy148.996