High tumor mutational burden (TMB) predicts not only response to immune checkpoint inhibitors (ICI) in advanced non-small cell lung cancer (NSCLC) but also immune-related toxicity. In this single-center cohort of 1,215 patients treated with ICI ± chemotherapy, higher baseline TMB was associated with an increased risk of immune-related adverse events (irAEs) and earlier onset; a very high TMB (≥19 mut/Mb, 90th percentile) was the strongest predictor of both outcomes. High‑TMB tumors were enriched for CD8+ T cells, supporting a biologically driven link between tumor immunogenicity and irAE risk. For CTSNet’s audience, the study positions very high TMB as a dual biomarker for ICI efficacy and toxicity in lung cancer, informing multidisciplinary discussions about patient selection, counseling, and monitoring of thoracic oncology patients receiving immunotherapy.
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Tumor Mutational Burden as a Predictor of Immune-Related Adverse Events in Patients With Advanced Non-Small Cell Lung Cancer Receiving Immune Checkpoint Inhibitors: A Brief Report
Submitted by: Akshay Patel
Source: Journal of Thoracic Oncology
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Author(s): Federica Pecci, Xinan Wang, Valentina Santo, Eleonora Gariazzo, Edoardo Garbo, Francesco Paoloni, Guilherme Rossato de Almeida, Mihaela Aldea, Alessandro Di Federico, Joao V. Alessi, Stephanie Canty, Giulia Bruschi, William Lotter, Mark M. Awad, Alexander Gusev, Narjust Florez, David C. Christiani, Scott J. Rodig, Mizuki Nishino, Pasi A. Jänne, Elad Sharon, Biagio Ricciuti
