Newly-diagnosed IDHwt MGMT unmethylated glioblastoma patients treated with standard radiation, nivolumab, and BMS-986205

The median overall survival (OS) was 11.5 months for all patients, with 4 individuals alive at ≥28 months, and 2 patients alive at 5 years post-diagnosis. Analysis of resected tumor at the time of first recurrence revealed intratumoral IDO1 expression to be primarily enriched in myeloid lineage cells. Higher systemic levels of naïve and early effector CD8+ T cells, higher systemic levels of microbial-derived aryl-lactates, lower systemic levels of microbial-derived aryl acetates, higher levels of fecal-derived Massilioclostridium coli, GGB3819-SGB5184, Dysosmobacter welbionis, Phocaeicola plebeius, an age of <65 years old, and patients who underwent subtotal but not gross total tumor resection, were significantly more likely to live past 28 months while on treatment.

This study provides a biological rationale for use of RT, PD-1 mAb, and IDO1 enzyme inhibitor treatment in temodar naïve GBM patients who survive well after 2 years while on treatment (ClinicalTrials.gov: NCT04047706).