7506 Background: The goal of PILLAR-2 (NCT00790036) was to reduce DLBCL relapse by providing 1 year of adjuvant EVE to poor-risk (International Prognostic Index [IPI] ≥3) pts who had achieved a CR with R-chemo. Methods: PILLAR-2 was a multicenter double-blind, placebo (PBO)-controlled, phase 3 study. Pts with histologically confirmed stage III/IV poor-risk (IPI ≥3) DLBLC who had a PET/CT-confirmed CR to first-line R-chemo were randomized 1:1 to EVE 10 mg/day or PBO for 1 year or until disease relapse, unacceptable toxicity, or death. The primary endpoint was disease-free survival (DFS) by local assessment using revised IWRC; secondary endpoints were overall survival (OS), lymphoma-specific survival (LSS), and safety. Results: Median study follow-up was 50.4 months (range, 24.0–76.9 months). Of the 742 pts randomized, 177 (48%) pts in the EVE and 249 (67%) in the PBO arms completed the study treatment as per protocol. Overall, 47% pts were ≥65 years, 50% were male and 42% had an IPI of 4+5. Adjuvant EVE did not improve DFS vs. PBO (Log-rank p = 0.276) (Table). The 2-yr DFS rates (95% CI) were 78% (73-82%) in EVE vs 77% (72-81%) in PBO. However, trends favoring EVE were observed for OS and LSS, and for exploratory analyses of DFS and OS in males and those with IPI 4+5. Common grade 3/4 AEs with > 3% difference for EVE vs PBO included neutropenia, stomatitis, CD4 lymphocytes decreased, lymphopenia and anemia. Conclusions: In poor-risk DLBCL patients with a CR after R-chemo,adjuvant EVE for 1 year did not improve DFS. A trend favoring EVE for OS and LSS, overall and for DFS in selected patient subgroups suggests that everolimus may provide anti-lymphoma activity in high-risk DLBCL, and warrant further investigation. Clinical trial information: NCT00790036. EVE vs PBO Hazard ratio (95% confidence interval) DFS* Overall (n = 742) 0.92 (0.69–1.22)† IPI 4+5 (n = 313) 0.65 (0.42–1.01) Male (n = 372) 0.68 (0.45–1.05) OS* Overall (n = 742) 0.75 (0.51–1.10) IPI 4+5 (n = 313) 0.63 (0.37–1.07) Male (n = 372) 0.55 (0.32–0.94) LSS* (n = 742) 0.64 (0.39–1.04) * Median duration not evaluable. †Log-Rank p = 0.276