Predictive biomarkers for immune-related adverse events: PD-L1% and somatic mutations.

Abstract

e14649 Background: Immune checkpoint inhibitors (ICIs) with anti-PD-L1 activity are a mainstay of therapy in the treatment of non-small cell lung cancer (NSCLC). Anti-PD-L1 therapy can unfortunately lead to immune-related adverse events (irAEs) via T-cell activation. This abstract seeks to identify irAE predictive biomarkers, examining PD-L1 expression and specific somatic mutations. Methods: A retrospective study was conducted at two Brown Health University hospitals, examining 400 patients with NSCLC who received immunotherapy from 2015 to 2024. In this review, 294 patients had either in-house gene paneling or a send-out expanded panel, while 106 patients had no somatic genetic testing done. Immunohistochemistry (IHC) staining for PD-L1% was performed for 309 patients; 91 patients did not have IHC done. Additional chart review was performed to determine whether specified irAEs were identified. Patients received immunotherapy with different treatment intents: neoadjuvant (N = 3), adjuvant (N = 27), curative with or without radiation therapy (RT) (N = 117), or palliative (N = 253). Results: Of the 400 patients reviewed, 173 (43%) had at least one reported irAE. The most commonly-reported irAEs were hypothyroidism (N = 27, 6.75%), colitis (N = 24, 6%), dermatitis (N = 24, 6%), hepatitis (N = 18, 4.5%), fatigue (N = 14, 3.5%), adrenal insufficiency (N = 10, 2.25%), nephritis (N = 9, 2.25%), pneumonitis (N = 8, 2%), and myocarditis (N = 7, 1.75%). The average PD-L1% and somatic mutations identified for the 3 most common irAEs are listed in the table below. The average PD-L1% obtained from those without irAEs was 29% (168/227 reported). Conclusions: PD-L1% did not differ appreciably among those with or without irAEs or across different irAEs. Further investigation is warranted to determine whether somatic TP53 mutations confer an increased irAE risk. ICI Toxicity ICI Hypothyroidism ICI Colitis ICI Dermatitis Average PD-L1 36% (20/27 reported) 34% (20/24 reported) 32% (21/24 reported) PD-L1 Range <1% to >90% <1% to 90% <1% to 100% Somatic Mutations TP53 (6), KRAS G12C (2), KRAS G12F (2), KRAS G12D (1), KRAS G12V (1), PTEN deletion (1), NFE2L2 (1), SMAD4 deletion (1), BRAF V600E (1), IDH2 (1), NKX2-1 (1), ALK rearrangement (1), RB1 (1), PDGFRA (1), KDR (1), KEAP1 (1), FBXW7 G423V (1), TERT (1), None (5) TP53 (6), KRAS G12D (2), ATM (2), KRAS G12V (1) , KRAS G12S (1), PIK3CA (2), SOX2 (1), MLL2 (1), ETV6 (1), ZNF703 (1), CTNNB1 (1), MYST3 (1), KRAS Q61H (1), ERBB2 (1), STK 11 (1), NFE2L2 (1), FGF12 (1), FGFR1 (1), RB1 (1), BRAF G469A (1), None (6) TP53 (5), KRAS G12C (4), KRAS G12V (2), PIK3CA (2), ESR1 (1), ATM (1), CCNE1 (1), KRAS Q61H (1), TERT promoter SNV, RB1 (1), SOX2 (1), BCL-2 (1), FAT1, MCL1 (1), NFKB1 (1), NKX2-1 (1), CDK12 (1), None (5) Treatment Intent Adjuvant (1), Curative (5), Curative with RT (5), Palliative (16) Adjuvant (1), Curative (1), Curative with RT (2), Palliative (20) Adjuvant (1), Curative (0), Curative with RT (4), Palliative (19)