Introduction: Glioma-induced lymphopenia and lymphocyte dysfunction are well-recognized factors contributing to immunosuppression in patients with glioblastoma (GBM). Despite a long history of studying this immunosuppression, there have been few reports demonstrating that lymphocyte dysfunction independently predicts patient outcomes. Immunosuppression is a particularly important factor for patients receiving immunotherapy. We, therefore, analyzed the impact of lymphopenia on outcomes of patients receiving an autologous tumor vaccine for recurrent GBM.
Methods: As part of a prospective, multi-centered, phase II study, patients with recurrent GBM received autologous vaccine after gross-total resection of their tumors. The primary clinical endpoint was overall survival. Pre-operative blood samples were taken from all patients to measure the complete blood count (CBC) and differential, including the absolute lymphocyte count (ALC). In this analysis, survival outcomes were evaluated relative to the median ALC by univariate Kaplan-Meier analysis and multivariate Cox proportional hazards modeling.
Results: A total of 41 patients with recurrent GBM underwent resection and received a median of 6 doses of autologous vaccine. Median overall survival for the entire cohort was 42.6 weeks (95% CI 34.7-50.5). The median ALC was 0.9 x10^3 cells/uL, with 27/41 (66%) patients having lymphopenia according to the clinical laboratory standard (ALC < 1.0). When stratifying patients by ALC relative to the median value, patients with an ALC = 0.9 had significantly improved survival compared to patients with an ALC < 0.9 (49.1 vs. 37.1 weeks; log-rank p=0.039). In a proportional hazards model including age, KPS, number of vaccine doses, and lymphocyte counts, an ALC = 0.9 was an independent positive predictor with a hazard ratio of 0.85 (95% CI 0.73-0.99, p=0.036).
Conclusions: Pretreatment lymphopenia may affect the outcomes of patients with recurrent GBM receiving immunotherapy. The implications of lymphopenia should be considered when selecting patients for future vaccine clinical trials.
Patient Care: Improved understanding of the factors that influence clinical outcomes for glioblastoma patients treated with immunotherapy will allow clinicians to better select patients for enrollment in therapy and may suggest new targets for therapy to improve outcomes.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) describe the effects of glioblastoma on lymphocyte counts and function, 2) describe the mechanism of action of adoptive immunotherapy for glioblasoma, 3) identify the impact of glioma-induce lymphopenia on immunotherapy outcomes