{
  "abstract": "Background Immune checkpoint inhibitors (ICIs) have rapidly transformed modern cancer care. However, most of the existing clinical literature on ICI outcomes have been derived from predominantly White patient populations, leaving the impact of race on immunotherapy response and immune-related adverse event (irAE) incidence insufficiently characterized. While Black individuals have a higher incidence of certain spontaneous autoimmune diseases, it remains unclear whether this predisposition influences the likelihood of developing irAEs in the setting of ICI therapy. To better characterize the impact of race on ICI outcomes, we profiled circulating cytokines and compared immunotherapy efficacy and safety by race.Methods We prospectively enrolled patients receiving standard-of-care ICI-based regimens for solid tumors at Johns Hopkins (IRB #00267960) and performed analysis of 39 cytokines using multiplex Luminex immunoassay on baseline plasma specimens. Clinical records were reviewed for demographic characteristics and clinical outcomes, including best response according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and irAEs using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Patients of races other than Black or White were excluded from this analysis.Results Our study cohort included 255 patients (Black, n=62; White, n=193). Most patients received ICI therapy for advanced/metastatic disease (86.7%) with single agent or combination ICI therapy (60.0%), while the remainder received ICI in combination with chemotherapy or targeted therapies. 88.6% of patients did not have baseline autoimmune disease. The incidence of any irAE was similar between groups (Black, 45%; White, 51%; χ 2 p=0.49), as was the rate of grade ≥3 irAEs (χ2 p=0.40), and distribution of irAEs (figure 1). In the subset of patients with measurable disease (Black n=55; White, n=147), overall response rate (ORR) was numerically higher in Whites patients (32.7% vs 20.0%, χ2 p=0.11), but not significant after controlling for clinical variables including tumor type (p=0.42). Cytokine analysis revealed significantly lower baseline levels of iTAC (adjusted p<0.001), MPIF-1 (adjusted p<0.001), and IL-22 (adjusted p=0.02) in Black patients compared to White patients (figure 2).Conclusions In this prospective cohort, which included 24% Black patients, a proportion far exceeding their typical representation in clinical trials, Black and White patients experienced comparable rates of ICI efficacy and toxicity. However, Black patients demonstrated distinct baseline cytokine profiles, including significantly lower levels of iTAC and MPIF-1, both associated with myeloid trafficking and Th1 responses. These findings highlight immunologic differences by race that may have biologic relevance and warrant further study in larger cohorts.Abstract 1040 Figure 1Incidence of the five most common immune-related adverse events (irAEs), stratified by race. Bars represent the proportion of patients experiencing each irAE among Black and White patients. Percentages reflect the incidence within each racial group. P values are derived from Fisher’s exact tests comparing irAE incidence between groupsAbstract 1040 Figure 2Baseline peripheral cytokines that significantly differed between Black and White patients. Comparisons were performed using the Wilcoxon rank-sum test, with p values adjusted for multiple comparisons using the Benjamini-Hochberg method",
  "authors": [
    {
      "affiliations": [
        "Newark, DE, USA"
      ],
      "name": "Sophia J Zhao"
    },
    {
      "affiliations": [
        "Johns Hopkins University School of Medicine, Baltimore, MD, USA"
      ],
      "name": "Howard L Li"
    },
    {
      "affiliations": [
        "Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA"
      ],
      "name": "Yasser Ged"
    },
    {
      "affiliations": [
        "Johns Hopkins University School of Medicine, Baltimore, MD, USA"
      ],
      "name": "Madelena Brancati"
    },
    {
      "affiliations": [
        "Johns Hopkins University School of Medicine, Baltimore, MD, USA"
      ],
      "name": "Caroline Ellis"
    },
    {
      "affiliations": [
        "Johns Hopkins University School of Medicine, Baltimore, MD, USA"
      ],
      "name": "Ervin Griffin"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "James M Leatherman"
    },
    {
      "affiliations": [
        "Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA"
      ],
      "name": "Chester J Kao"
    },
    {
      "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": "Evan J Lipson"
    },
    {
      "affiliations": [
        "Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA"
      ],
      "name": "Julie R Brahmer"
    },
    {
      "affiliations": [
        "Genentech, Hoboken, NJ, USA"
      ],
      "name": "Laura Tang"
    },
    {
      "affiliations": [
        "Genentech, Pearland, TX, USA"
      ],
      "name": "Sanjay Bansal"
    },
    {
      "affiliations": [
        "Genentech, San Jose, CA, USA"
      ],
      "name": "Aditi Guha"
    },
    {
      "affiliations": [
        "F. Hoffmann-La Roche Ltd, Basel, Switzerland"
      ],
      "name": "Rajat Mohindra"
    },
    {
      "affiliations": [
        "Genentech/Roche, Basel, Switzerland"
      ],
      "name": "G Scott Chandler"
    },
    {
      "affiliations": [
        "Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA"
      ],
      "name": "Mark Yarchoan"
    },
    {
      "affiliations": [
        "Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA"
      ],
      "name": "Mari Nakazawa"
    }
  ],
  "title": "1040 Racial differences in peripheral cytokine signature do not lead to differences in immunotherapy outcome or toxicity",
  "uid": "26a7a8a5-3e7a-5e1a-8824-e6df8b4956d1"
}