{
  "abstract": "Background Recurrent glioblastoma (rGBM) remains uniformly lethal, with median survival measured in months despite multimodal therapy. Although pembrolizumab produces durable responses in other solid malignancies, activity in rGBM has been disappointing. Emerging data from melanoma, lung, and renal cancers suggest that treatment-induced or disease-related lymphopenia correlates with inferior outcomes on checkpoint inhibition. Because rGBM patients frequently receive lymphocyte-suppressive corticosteroids and chemoradiation, we asked whether a low pre-treatment absolute lymphocyte count (ALC) identifies a subgroup unlikely to benefit from pembrolizumab.Methods We performed a single-center retrospective study of adults with rGBM who received ≥1 dose of pembrolizumab between 1 May 2018 and 31 January 2025 and had lymphocyte counts available at our center. Demographics, MGMT status, prior bevacizumab exposure, dexamethasone use at initiation, and baseline ALC were abstracted from electronic records. Overall survival (OS) was defined as the time from the date of pembrolizumab initiation to the date of death from any cause or last follow up. Median OS (mOS) was calculated with Kaplan-Meier methods, and survival curves were compared with the log-rank test; an exploratory subgroup analysis stratified patients by bevacizumab exposure status. Low ALC was defined as <750 cells/mm 3 in this analysis.Results Forty-three patients met eligibility criteria (median age 59 years, 51% male) and 26% (n = 11) with MGMT methylation. Sixteen patients were bevacizumab-naïve and twenty-seven were bevacizumab-refractory. Across the entire cohort, baseline ALC<750 cells/mm 3 was associated with significantly shorter OS compared to baseline ALC≥750 cell/mm3 (3.4 vs 8.5 months, p=0.0048) with a slightly higher proportion of patients on dexamethasone in low ALC group (75% vs 52%). Among bevacizumab-naïve patients (n=16), mOS was 9.7 months; within this subgroup, patients with ALC<750 cells/mm3 demonstrated a trend toward shorter OS (4 vs. 11 months, p = 0.056) and had slightly higher dexamethasone exposure (80% vs. 55%). In the bevacizumab-refractory group, mOS was 4.3 months; again, low ALC trended toward a shorter OS (2.6 vs 7 months; p=0.075) with similar rates of dexamethasone use (73% vs 50%).Conclusions Baseline lymphopenia preceding pembrolizumab treatment is associated with shorter mOS in patients with rGBM. While the sample size was limited, the consistency of trends across subgroups highlights the need for further validation in larger patient cohorts.",
  "authors": [
    {
      "affiliations": [
        "Department of Oncology, Mayo Clinic, Rochester, MN, USA"
      ],
      "name": "Md Al Amin"
    },
    {
      "affiliations": [
        "Department of Pharmacy, Mayo Clinic, Rochester, MN, USA"
      ],
      "name": "Sydney E Schultz"
    },
    {
      "affiliations": [
        "Department of Pharmacy, Mayo Clinic, Rochester, MN, USA"
      ],
      "name": "Riley T Mohr"
    },
    {
      "affiliations": [
        "Department of Oncology, Mayo Clinic, Rochester, MN, USA",
        "Department of Biomedical Science, University of Guelph, Guelph, ON, Canada"
      ],
      "name": "Justin Tang"
    },
    {
      "affiliations": [
        "Department of Oncology, Mayo Clinic, Rochester, MN, USA"
      ],
      "name": "Hongzhi Dong"
    },
    {
      "affiliations": [
        "Department of Oncology, Mayo Clinic, Rochester, MN, USA"
      ],
      "name": "Nishika Karbhari"
    },
    {
      "affiliations": [
        "Department of Oncology, Mayo Clinic, Rochester, MN, USA"
      ],
      "name": "Jian L Campian"
    }
  ],
  "title": "407 Relationships between lymphocyte counts and clinical outcomes in patients with recurrent glioblastoma treated with pembrolizumab",
  "uid": "8ec5143e-2171-517a-8a40-a9fc9543642c"
}