{
  "abstract": "Background Neurologic immune-related adverse events (n-irAEs) are rare, but potentially morbid toxicities, occurring in ~1-8% of patients receiving immunotherapy. Prognostic and predictive biomarkers are lacking. We hypothesize that distinct clinical or laboratory features at presentation may help identify patients with advanced urinary cancers at risk of developing severe n-irAEs requiring hospitalization.Methods We reviewed records of 23 patients with documented n-irAEs admitted through the emergency department to the Genitourinary Medical Oncology service at MD Anderson between 05/2022 and 02/2025. We excluded patients with neuromuscular toxicity (n=5) due to characterization in previous efforts. 1 Diagnosis was confirmed by a neuro-oncologist after excluding other etiologies.Results Eighteen patients were eligible for analysis and classified as having central nervous system (CNS)-type (n=7) or peripheral nervous system (PNS)-type (n=11) n-irAEs. Baseline characteristics and diagnostic workflows are summarized in table 1 and figure 1, respectively. Sixteen (88.9%) patients underwent lumbar puncture. Among them, approximately one-third showed either lymphocytic pleocytosis, elevated IgG/albumin ratio, or detectable myelin basic protein. Cerebrospinal fluid (CSF) protein levels were available in 15; nine (60%) were elevated. Baseline serum cytokine analysis revealed elevated median IFN-γ (2.3× ULN [IQR: 0.6–10.1]) and IL-6 (3× ULN [IQR: 1.6–4.5]) levels, with median TNF-α levels remaining near normal (0.9× ULN [IQR: 0.75–1.8]) (Kruskal-Wallis test, p=0.026). These patterns were consistent across CNS and PNS subtypes. Inpatient management included IV corticosteroids (16, 88.9%), five sessions of plasmapheresis (15, 83.3%), and biologic agents (14, 77.8%). Twelve patients (66.7%) experienced clinical improvement, defined as partial or complete resolution of neurological symptoms, while six (33.3%) did not experience amelioration despite treatment. Post-hospitalization outcomes consisted of home discharge (13, 72.2%), hospice (2, 11.1%), rehabilitation/assisted living facilities (2, 11.1%), and death (1, 5.6%). Most patients were alive at six months after discharge, and only four (22.2%) patients expired within 6 months (three of which were diagnosed with ICI-induced encephalitis). Median overall survival from ED presentation was shorter in patients with elevated CSF protein (19.7 months [95% CI: 0.6-NE]) versus those with normal levels (not reached) (HR=5.5 [95% CI: 0.9–34] p=0.06).Conclusions Elevated CSF protein levels may be reflective of inflammation severity. However, further analysis of CSF protein levels is warranted in larger samples. Elevated serum IL-6 and IFN-γ may point toward potential immune mechanisms of pathogenesis of these n-irAEs implicating T cells and myeloid cells – supporting further investigation of immune cell phenotyping and cytokine targeting in larger cohorts and other solid tumors.Reference Siddiqui BA, Palaskas NL, Basu S et al. Molecular pathways and cellular subsets associated with adverse clinical outcomes in overlapping immune-related myocarditis and myositis. Cancer Immunol Res. 2024;12(8):964–987.Ethics Approval The study was performed in accordance with PA16-0736 protocol, approved by MD Anderson Cancer Center Institutional Review Board. The protocol is an investigational low-risk study with consent waiver for all participants (retrospective series with no identifiable patient information or clinical care-changing information).Consent The study was performed in accordance with PA16-0736 protocol, approved by MD Anderson Cancer Center Institutional Review Board. The protocol is an investigational low-risk study with consent waiver for all participants (retrospective series with no identifiable patient information or clinical care-changing information).Abstract 1064 Table 1Baseline characteristics of cohort (n=18)Abstract 1064 Figure 1Relevant diagnostic evaluation and clinical characteristics (n=18)",
  "authors": [
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA",
        "Baylor College of Medicine, Houston, TX, USA"
      ],
      "name": "Mohammad Jad Moussa"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Cindy A Jiang"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Sheeba Varughese"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Anishia Rawther-Karedath"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Hongchao He"
    },
    {
      "affiliations": [
        "Baylor College of Medicine, Houston, TX, USA"
      ],
      "name": "Saivaroon Gajagowni"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Emanuele Crupi"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Zachariah Thomas"
    },
    {
      "affiliations": [
        "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Amishi Y Shah"
    },
    {
      "affiliations": [
        "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Andrew W Hahn"
    },
    {
      "affiliations": [
        "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Nizar M Tannir"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA",
        "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Pavlos M Msaouel"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Sumit K Subudhi"
    },
    {
      "affiliations": [
        "The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Bilal A Siddiqui"
    },
    {
      "affiliations": [
        "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Matthew T Campbell"
    },
    {
      "affiliations": [
        "Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Ashley Aaroe"
    },
    {
      "affiliations": [
        "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"
      ],
      "name": "Omar Alhalabi"
    }
  ],
  "title": "1064 Clinical and prognostic characterization of high-grade neurologic immune-related adverse events in patients with urinary cancers",
  "uid": "022d4be4-4a86-5a2f-89d1-cfe59b5c1bc4"
}