Class II HLA-DRB4 is a predictive biomarker for survival following immunotherapy in metastatic non-small cell lung cancer.

Autor: Jiang CY; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.; Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhao L; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA., Green MD; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA., Ravishankar S; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Towlerton AMH; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Scott AJ; Division of Clinical Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Raghavan M; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA., Cusick MF; Department of Pathology, University of Michigan, Ann Arbor, MI, USA., Warren EH; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Ramnath N; Lieutenant Colonel Charles S. Kettles VA Medical Center (VA Ann Arbor Health System), 2215 Fuller Ave, Ann Arbor, MI, 48105, USA. nithyar@med.umich.edu.; Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. nithyar@med.umich.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Jan 03; Vol. 14 (1), pp. 345. Date of Electronic Publication: 2024 Jan 03.
DOI: 10.1038/s41598-023-48546-y
Abstrakt: Immune checkpoint inhibitors (ICI) are important treatment options for metastatic non-small cell lung cancer (mNSCLC). However, not all patients benefit from ICIs and can experience immune-related adverse events (irAEs). Limited understanding exists for germline determinants of ICI efficacy and toxicity, but Human Leukocyte Antigen (HLA) genes have emerged as a potential predictive biomarker. We performed HLA typing on 85 patients with mNSCLC, on ICI therapy and analyzed the impact of HLA Class II genotype on progression free survival (PFS), overall survival (OS), and irAEs. Most patients received pembrolizumab (83.5%). HLA-DRB4 genotype was seen in 34/85 (40%) and its presence correlated with improved OS in both univariate (p = 0.022; 26.3 months vs 10.2 months) and multivariate analysis (p = 0.011, HR 0.49, 95% CI [0.29, 0.85]). PFS did not reach significance (univariate, p = 0.12, 8.2 months vs 5.1 months). Eleven patients developed endocrine irAEs. HLA-DRB4 was the predominant genotype among these patients (9/11, 81.8%). Cumulative incidence of endocrine irAEs was higher in patients with HLA-DRB4 (p = 0.0139). Our study is the first to suggest that patients with metastatic NSCLC patients on ICI therapy with HLA-DRB4 genotype experience improved survival outcomes. Patients with HLA-DRB4 had the longest median OS (26.3 months). Additionally, we found a correlation between HLA-DRB4 and the occurrence of endocrine irAEs.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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