Abstract 1402: Comparative analysis of clinicopathologic features and tumor immune-microenvironment of primary diffuse large B cell lymphoma of the central nervous system according to molecular classification

Abstract Background: Recently, molecular classification is gradually applied to systemic diffuse large B cell lymphoma (DLBCL) for predicting prognosis and targeted therapy. Still, little is known about molecular classification and its clinicopathologic impacts in primary CNS-DLBCL (PCNS-DLBCL). Methods: Next genetic sequencing (NGS) and then LymphGen classification were done in 62 PCNS-DLBCL patients with homogenous R-MVP therapy. Immunohistochemistry of CD8, FOXP3, PD-1, CD68, CD163 and PD-L1 was performed and enumeration of CD8+, Foxp3+ and PD-1+ tumor infiltrating lymphocytes (TILs) and CD68+ and CD163+ macrophages was done by Aperio ImageScope 12.4.3. Tumoral PD-L1 expression was manually evaluated. Results: One A53, 1 EZB, 1 ST2, 2 MCD/A53, 43 MCD and 14 other (unclassified) subtypes were identified. As expected, MCD subtype was predominant in PCNS-DLBCL (69.4%). MCD and MCD/A53 subtypes were correlated with older age (P=0.001), higher MSKCC class (2-3) (P=0.014), and tumor multiplicity (P=0.004), compared to non-MCD subtypes. However, there was no significant difference in progression-free survival (PFS) and overall survival (OS) between two groups. Other clinicopathologic parameters including sex, performance status, B symptom, elevated LDH, ocular or multiple involvement and Ki-67 labeling index showed no significant difference between two groups. In addition, CD8+ TILs, PD-1+ TILs, FOXP3+ TILs, FOXP3+/CD8+ ratio, PD-1+/CD8+ ratio, CD68+, CD163+ and tumoral PD-L1 expression were not different according to molecular subtype. Of note, tumoral PD-1 expression was found in 16.7% of PCNS-DLBCLs including MCD (4/36, 11.1%) and non-MCD subtypes (4/12, 33.3%), which was much higher than systemic DLBCL (6/121, 4.96% in our previous data). Cases with tumoral PD-1 expression showed worse PFS than others (P=0.029). At single gene alteration level, both of MYD88L265P and CD79B mutation and BCL7A mutation tended to be related to poor PFS (P=0.067 and P=0.105, respectively). CDKN2A deletion, TP53 mutation and CD79A mutation tended to be related to poor OS (P=0.075, P=0.104, and P=0.107, respectively). Conclusions: This is the first reporting molecular classification and their clinical significance in PCNS-DLBCL of Asian population. MCD subtype was prevalent but has no prognostic power in PCNS-DLBCL. Further larger study is needed. Citation Format: Sehui Kim, Jeemin Yim, Bogyeong Han, Sung-Hye Park, Jiwon Koh, Hongseok Yun, Tae Min Kim, Yoon Kyung Jeon. Comparative analysis of clinicopathologic features and tumor immune-microenvironment of primary diffuse large B cell lymphoma of the central nervous system according to molecular classification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1402.