RTHP-43 (LTBK-02). MULTI-TIME POINT EVALUATION OF PERIPHERAL BLOOD MYELOID-DERIVED SUPPRESSOR CELL AND LYMPHOCYTE POPULATIONS IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA RECEIVING ADJUVANT THERAPY

Alterations in peripheral blood cell populations, including myeloid cell subsets and lymphocytes, have been associated with poor prognostic outcomes in patients with glioblastoma (GBM). To date, evaluation of these populations has largely been on freeze-thawed samples at a limited number of time points. The purpose of our study is to identify the frequency and activation status of tumor-supportive myeloid and lymphocyte subsets during the course of standard adjuvant therapy in patients with GBM in fresh peripheral blood samples. We hypothesize that dysfunctional myeloid and lymphocyte populations expand during standard care temozolomide (TMZ)/radiation therapy (RT). We prospectively enrolled 16 patients with a new diagnosis of GBM that underwent maximal safe surgical resection. Twelve received standard adjuvant therapy consisting of six weeks of TMZ/RT. Four received alternative therapies: one experimental chemotherapeutic/three alternative radiation schemes. Peripheral blood was obtained seven times over the course of adjuvant therapy: prior to starting adjuvant therapy, five during treatment, and once one month after completion of therapy. Eleven patients completed all seven time points. Peripheral blood samples were analyzed by flow cytometry, focusing on immune checkpoints and critical markers of activation of systemic immunity. Available preliminary data demonstrate a median increase of 2.1% (-21.2–27.4%) in the frequency (%fx) of myeloid-derived suppressor cells (MDSC) after commencement of adjuvant therapy at time point 2 (TP2), compared to baseline. To date, 7/16 patients are alive and without evidence of recurrent disease on imaging. The majority of these patients had a decrease in %fx of MDSC at TP2, after starting adjuvant therapy, compared to baseline. The %fx of CD8+ T cells was greatest at TP7 (range: 21.7%-67.0%), one month after TMZ/RT, for most patients. PD-1 and FOXP3 expression by lymphocytes was variable across time points, suggesting the importance of additional factors which will be explored through future analyses. These early findings suggest that the immune response changes throughout the course of TMZ/RT. An understanding of these changes in the peripheral blood, termed immunodynamics in the context of our studies, may be valuable future tool to aid in optimizing immunity in patients with GBM.