Outcomes of patients with glioblastoma multiforme (GBM) with lymphopenia.

e14053 Background: Lymphopenia has been associated with adverse survival outcomes in multiple solid tumors; however, its prognostic significance in glioblastoma (GBM) has limited and conflicting data. Given the immunomodulatory effects of temozolomide (TMZ), understanding the relationship between treatment-related lymphopenia and survival outcomes may inform prognosis and therapeutic decisions. This study evaluates the association between lymphopenia and progression-free survival (PFS) and overall survival (OS) in patients with GBM treated with TMZ. Methods: We performed a retrospective chart review of adult patients (≥18 years) with biopsy-proven GBM diagnosed between January 1, 2019, and December 31, 2023, at a single institution. All eligible patients had received at least 1 dose of TMZ. Patients with pre-existing lymphopenia, prior radiation therapy, or comorbid conditions known to cause lymphopenia were excluded. Lymphopenia was defined as an absolute lymphocyte count <1.0 × 10⁹/L. Cox proportional hazards regression analyses were used to assess associations with OS and PFS. Statistical significance was defined as p < 0.05. Multivariate analysis adjusted for MGMT promoter methylation, maintenance therapy use, ECOG status and smoking status. Results: A total of 27 patients were included. The cohort was 48% female, 96% White, and 74% never smokers; 85% had an ECOG status of 0–1 and 44% had MGMT promoter methylation. Treatment-related lymphopenia was associated with hazard ratios (HR) of 0.22 for OS and 0.75 for PFS; however, these findings were not statistically significant. Receipt of maintenance TMZ showed statistically significant association with improved OS (HR 0.22) and PFS (HR 0.25). MGMT promoter methylation was associated with improved PFS (HR 0.67) but not OS (HR 2.47), without statistical significance. Conclusions: In this single-institution retrospective analysis, treatment-related lymphopenia was not significantly associated with PFS or OS in patients with GBM treated with TMZ. In contrast, receipt of maintenance TMZ emerged as a strong independent predictor of improved survival outcomes, reinforcing its continued importance within standard-of-care management. Although limited by sample size, these findings suggest that treatment-related lymphopenia alone may not represent a reliable prognostic biomarker in GBM and may provide clinical reassurance that lymphopenia observed during standard temozolomide-based therapy does not independently confer worse survival outcomes. Larger, prospective studies are warranted to further define immune-related predictors of outcome and to inform risk-adapted, biomarker-driven therapeutic strategies. Multivariate Cox analysis for OS and PFS. PFS HR PFS P-value OS HR OS P-Value Lymphopenia 0.75 0.77 0.22 0.16 Maintenance therapy recipients 0.25 0.02 0.22 0.02 MGMT methylation 0.67 0.40 2.47 0.10