Impact of VT-EBV-N on disease-free survival as post-remission therapy in EBV-positive extranodal NK/T-cell lymphoma: A randomized, double-blind, placebo-controlled phase 2 study.

7005 Background: Extranodal NK/T-cell lymphoma (ENKL) is an aggressive EBV-associated malignancy. Although complete remission (CR) can be achieved with intensive therapy, patients with high-risk features remain at substantial risk of relapse, and no standard post-remission therapy exists. VT-EBV-N is an autologous EBV-specific cytotoxic T lymphocyte (EBV-CTL) therapy designed to eliminate residual EBV-infected malignant cells. This phase 2 study evaluated the efficacy and safety of VT-EBV-N as post-remission therapy in patients with EBV-positive ENKL. Methods: This randomized, double-blind, placebo-controlled phase 2 trial enrolled patients with EBV-positive ENKL who had achieved CR within 6 months prior to enrollment and had at least one predefined high-risk factor for relapse. Patients were randomly assigned (1:1) to receive VT-EBV-N or autologous peripheral blood mononuclear cells (PBMC) as control. Treatment was administered IV weekly for 4 weeks, followed by a 4-week rest, and then once weekly for an additional 4 weeks (total 8 doses). The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. Efficacy was analyzed in the full analysis set (FAS), and safety was assessed in the safety set. Results: A total of 50 patients were randomized, and 46 patients (VT-EBV-N, n=21; control, n=25) were included in the FAS. Baseline characteristics and distributions of high-risk features were generally balanced between groups. At 2 years, VT-EBV-N demonstrated a clinically meaningful and significant improvement in DFS compared with control (95.0% vs 77.6%). DFS events occurred in 1/21 patients (4.8%) in the VT-EBV-N group and 8/25 patients (32.0%) in the control group. Stratified log-rank analysis confirmed a significant DFS benefit with VT-EBV-N (p=0.0347). No deaths occurred in the VT-EBV-N group, whereas 4 deaths (16.0%) were observed in the control group; the difference in OS did not reach statistical significance (p=0.0580). VT-EBV-N was generally well tolerated. Most adverse events (AEs) were grade 1–2. Grade ≥3 AEs (CTCAE) occurred in 2/21 patients (9.52%) in the VT-EBV-N group and 4/25 patients (16.00%) in the control group. No treatment-related deaths were reported. Conclusions: VT-EBV-N demonstrated a clinically meaningful improvement in disease-free survival with a favorable safety profile in patients with EBV-positive ENKL in complete remission and at high risk of relapse. These findings support VT-EBV-N as a promising post-remission therapeutic option for this rare and aggressive lymphoma. Clinical trial information: KCT0003592. Key efficacy and safety outcomes. Outcome VT-EBV-N Control (PBMC) Patients analyzed (FAS), n 21 25 2-year DFS, % 95.0 77.6 DFS events, n (%) 1 (4.8) 8 (32.0) Deaths, n (%) 0 (0.0) 4 (16.0) Grade ≥3 AEs, n (%) 2 (9.52) 4 (16.00)