VT-EBV-N Shows 95% Durable Disease-Free Survival in EBV-Positive ENKTL: Phase II Data at EHA 2026
核心洞察
The phase II VT-EBV-201 trial demonstrated a 2-year DFS rate of 95.0% with VT-EBV-N versus 77.6% with PBMC control in patients with EBV-positive ENKTL in complete remission.
At 4 years, DFS remained 95.0% for VT-EBV-N compared with 56.3% for the control arm, with a hazard ratio of 0.13 (p = 0.021).
Overall survival at 2 and 4 years was 100% in the VT-EBV-N arm versus 88.0% and 83.8% in the control arm, respectively (p = 0.0205).
Results from the randomized, double-blind, placebo-controlled, multicenter phase II VT-EBV-201 trial (NCT03671850) show that VT-EBV-N, an autologous Epstein–Barr virus (EBV)-specific cytotoxic T-lymphocyte (CTL) therapy, delivered durable disease-free survival (DFS) as post-remission therapy in patients with EBV-positive extranodal natural killer/T-cell lymphoma (搜索) (ENKTL). The findings were presented by Deok-Hwan Yang, MD, PhD, of Chonnam National University Hwasun Hospital (搜索) in Gwangju, South Korea, at the European Hematology Association (EHA) 2026 Congress, held June 11–14, 2026, in Stockholm, Sweden.
The study enrolled 48 patients with ENKTL who had achieved complete remission (CR) within 6 months prior to enrollment. Participants were randomized 1:1 to receive VT-EBV-N (n = 21) or autologous peripheral blood mononuclear cells (PBMCs; n = 25) as control. The primary endpoint was 2-year DFS.
Durable DFS advantage with VT-EBV-N
The 2-year DFS rate was 95.0% (95% CI, 69.5–99.3) in the VT-EBV-N arm compared with 77.6% (95% CI, 54.2–90.0) in the PBMC control arm. At 4 years, the DFS rate remained 95.0% (95% CI, 69.5–99.3) with VT-EBV-N, while the control arm declined to 56.3% (95% CI, 31.0–75.4), yielding a hazard ratio of 0.13 (95% CI, 0.02–1.02; p = 0.021). The total number of DFS events was 1 in the investigational arm versus 9 in the control arm, with 2 patients in the control arm dying due to a DFS event.
"VT-EBV-N showed durable benefit, with a 2-year and 4-year DFS rate of 95.0% compared with 77.6% and 56.3% in the control group, respectively," Yang stated during the presentation.
Overall survival reaches 100% at 4 years
Overall survival (OS) findings similarly favored VT-EBV-N. At both 2 and 4 years, OS was 100% in the VT-EBV-N arm. In the control arm, OS rates were 88.0% (95% CI, 67.3–96.0) at 2 years and 83.8% (95% CI, 62.4–93.6) at 4 years. Six OS events occurred in the control arm (p = 0.0205).
Favorable safety profile
VT-EBV-N demonstrated a manageable safety profile consistent with its mechanism as an autologous CTL therapy. Any-grade adverse events (AEs) occurred in 76% of patients in both arms. Grade 3 or higher AEs were reported in 10% of patients receiving VT-EBV-N versus 16% in the control arm. Serious AEs occurred in 19% versus 28%, respectively.
Notably, no grade 3 or higher adverse drug reactions (ADRs) or serious ADRs were observed with VT-EBV-N. One patient in the VT-EBV-N arm experienced ADRs, which included grade 2 back pain and grade 1 myalgia. The most common AEs in the VT-EBV-N arm were COVID-19 infection (n = 5) and upper respiratory tract infection (n = 3).
"VT-EBV-N demonstrated a favorable and manageable safety profile as post-remission therapy, with no grade 3 or greater treatment-related adverse events observed," Yang noted. "This study provides robust evidence supporting VT-EBV-N as an effective consolidation strategy for relapse prevention."
Study design and patient population
Patients were enrolled across 13 sites in Korea from April 2019 to April 2023. Eligible patients had ENKTL in CR within 6 months of enrollment, Ann Arbor stage II to IV disease, locally invasive disease, and elevated lactate dehydrogenase. Those in the investigational arm received intravenous VT-EBV-N at 4 × 10⁷ cells/bag weekly for up to 4 weeks, followed by a 4-week treatment holiday, and then for an additional 4 weeks. PBMC was administered at the same dose and schedule.
The median age was 56.52 years (SD, 10.0) in the VT-EBV-N arm and 57.12 years (SD, 13.0) in the control arm. Most patients had Ann Arbor stage II/IIE disease (66.7% vs 68.0%), received one prior line of chemotherapy (85.7% vs 88.0%), and had intermediate-risk PINK-E status (71.4% vs 92.0%). VT-EBV-N showed benefit across most relevant patient subgroups.
Background and rationale
ENKTL has shown sensitivity to radiotherapy and improved outcomes with non-anthracycline-based chemotherapy, yet evidence-based standard post-remission therapy has remained an unmet need. VT-EBV-N was designed as an autologous EBV-specific CTL therapy to eliminate residual EBV-infected malignant cells. A previous investigator-initiated study (KCT0001271) demonstrated that among 10 patients with ENKTL treated with EBV latent membrane protein (LMP)-1 and LMP-2a-specific cytotoxic T cells, no serious AEs were observed, with 9 of 10 maintaining progression-free status and all remaining alive at 4-year follow-up.
Yang acknowledged several study limitations, including the need for additional subgroup analyses, biomarker and translational analyses, patient-reported outcome data, and longer-term follow-up to confirm survival outcomes. He also noted the importance of extending the trial to include a more diverse study population and conducting further studies to clarify the mechanism of action for VT-EBV-N.