{
  "abstract": "Background Immune-related adverse events (irAEs) are a common and sometimes severe complication of immune checkpoint inhibitor (ICI) therapy. Identifying baseline risk factors for irAEs is essential to improve patient selection and guide treatment decisions. A prior studies indicated that the IL7 polymorphism rs16906115 may increase irAE risk in melanoma and renal cell carcinoma (RCC) patients treated with ICIs.Methods We prospectively enrolled patients with solid tumors receiving ICIs and systematically graded irAEs using CTCAE v5.0. Germline DNA was extracted from peripheral blood mononuclear cells and genotyped using the Illumina Infinium Global Screening Array v3.0 (~665,000 markers). A candidate SNP analysis was conducted using a panel of 200 variants previously associated with autoimmune diseases. Associations between SNP carriage and irAE development (any grade and ≥ grade 3), as well as ICI response, were evaluated.Results Among 170 patients, 52% developed any-grade irAEs and 23% experienced grade ≥3 irAEs. The IL7 rs16906115 variant was present in 36% of patients without irAEs, 29% with any irAE, and 23% with grade ≥3 irAEs, with no significant association observed. Several autoimmune-associated variants, including rs13330176, rs6426833, rs762421 (non-coding regions), and rs3197999 (MST1), showed nominal associations with irAEs, but none remained significant after multiple testing correction ( figure 1). Multiple SNP variants previously linked to spontaneous autoimmune colitis were not associated with ICI-induced colitis. Autoimmune risk allele burden scores were not associated with irAE occurrence, severity, or therapeutic response.Conclusions In this prospective pan-tumor cohort, germline variants associated with spontaneous autoimmune diseases were not significantly linked to irAE development or ICI efficacy. These findings suggest that the genetic architecture underlying irAEs may differ from that of idiopathic autoimmunity. Although exploratory and limited by sample size, our data suggest that the presence of known autoimmune risk alleles should not preclude patients from receiving ICI therapy.Abstract 1046 Figure 1Manhattan plot with top SNPs. Autoimmune single nucleotide polymorphisms possibly associated with immune related adverse events",
  "authors": [
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Rohan Verma"
    },
    {
      "affiliations": [
        "Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA"
      ],
      "name": "Mari Nakazawa"
    },
    {
      "affiliations": [
        "Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA"
      ],
      "name": "Chester J Kao"
    },
    {
      "affiliations": [
        "Johns Hopkins University School of Medicine, Baltimore, MD, USA"
      ],
      "name": "Howard L Li"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Madelena Brancati"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Evan J Lipson"
    },
    {
      "affiliations": [
        "Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA"
      ],
      "name": "Yasser Ged"
    },
    {
      "affiliations": [
        "Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA"
      ],
      "name": "Marina Baretti"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Brit Adler"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Tanguy Y Seiwert"
    },
    {
      "affiliations": [
        "Johns Hopkins University School of Medicine, Baltimore, MD, USA"
      ],
      "name": "Jean Hoffman-Censits"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Burles Johnson"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Laura Cappelli"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Daniel J Zabransky"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Won Jin Ho"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Govind Warrier"
    },
    {
      "affiliations": [
        "Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA"
      ],
      "name": "Julie R Brahmer"
    },
    {
      "affiliations": [
        "Genentech, San Francisco, CA, USA"
      ],
      "name": "Cameron Adams"
    },
    {
      "affiliations": [
        "Genentech, San Francisco, CA, USA"
      ],
      "name": "Laura Tang"
    },
    {
      "affiliations": [
        "F. Hoffmann-La Roche Ltd, Basel, Switzerland"
      ],
      "name": "Rajat Mohindra"
    },
    {
      "affiliations": [
        "Genentech/Roche, Basel, Switzerland"
      ],
      "name": "G Scott Chandler"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Aliyah Pabani"
    },
    {
      "affiliations": [
        "Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA"
      ],
      "name": "Mark Yarchoan"
    }
  ],
  "title": "1046 Autoimmune risk alleles do not contraindicate immune checkpoint inhibitor use: findings from a prospective pan-tumor cohort",
  "uid": "46b2cde9-22e9-5cc5-8f1c-9a0b44e19f6e"
}