VT-EBV-N Yields Durable Disease-Free Survival in Pretreated ENKTL

VT-EBV-N displayed durable disease-free survival (DFS) compared with plasma blood mononuclear cell (PBMC) therapy among patients with Epstein-Barr virus (EBV)–positive extranodal natural killer (NK)/T-cell lymphoma (ENKTL)who experienced a complete remission (CR) within 6 months prior to enrollment, according to an oral presentation of a phase 2 study (NCT03671850) presented at the European Hematology Association (EHA) 2026 Congress.¹

Findings from the study demonstrated a significant DFS advantage with VT-EBV-N among these patients, with a 2-year DFS rate of 95.0% (95% CI, 69.5%-99.3%) among 21 patients vs 77.6% (95% CI, 54.2%-90.0%) among 25 patients treated in the control group with PBMC. Moreover, the 4-year rates were 95.0% (95% CI, 69.5%-99.3%) and 56.3% (95% CI, 31.0%-75.4%), respectively. The total number of DFS events in each arm were 1 and 9, respectively, with 2 patients having died due to a DFS event in the control arm (P = .021).

Moreover, the overall survival (OS) findings favored the investigational therapy vs the control arm, with OS rates of 100% (95% CI, not evaluable [NE]-NE) vs 88.0% (95% CI, 67.3%-96.0%) at 2 years and 100% (95% CI, NE-NE) vs 83.8% (95% CI, 62.4%-93.6%) at 4 years, respectively. There were 6 OS events in the control arm (P = .0205).

VT-EBV-N showed benefit across most relevant patient subgroups, and between-arm differences did not reach significance, with plasma cytokine levels trending higher in VT-EBV-N.

“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,” Deok-Hwan Yang, MD, PhD, researcher in the Department of Hemato-Oncology of Chonnam National University Hwasun Hospital in Gwangju, South Korea, stated in the presentation.¹ “VT-EBV-N demonstrated a favorable and manageable safety profile as post-remission therapy, with no grade [3 or greater] treatment-related adverse events [TRAEs] observed…this study provides robust evidence supporting VT-EBV-N as an effective consolidation strategy for relapse prevention.”

In the phase 2 protocol, patients with ENKTL in CR within 6 months of enrollment, Ann Arbor stage II to IV disease, locally invasive disease, and elevated lactate dehydrogenase were randomly assigned 1:1 to received VT-EBV-N or control with PBMC. Patients were enrolled across 13 sites in Korea from April 2019 to April 2023.

Those in the investigational arm received intravenous VT-EBV-N at 4 x 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 for the same dosing schedule. CT scans occurred starting at 3 weeks and occurred every 13 weeks thereafter until the 2-year follow-up period.

The median age in the investigational and control arms was 56.52 years (SD, 10.0) and 57.12 years (SD, 13.0), respectively, with 38.1% and 44.0% being 60 years and older at initial diagnosis. A total of 57.1% vs 76.0% were male, 57.1% vs 68.0% had an ECOG performance status of 0, and 90.5% vs 100% had nasal type disease. Most patients had Ann Arbor stage II/IIE disease (66.7% vs 68.0%), received 1 prior line of chemotherapy (85.7% vs 88.0%), and had intermediate-risk PINK-E status (71.4% vs 92.0%).

The primary end point of the study was 2-year DFS. Secondary end points included OS and DFS up to 4 years, as well as safety measures including AEs, vital signs and body weight, and laboratory tests. Exploratory end points included EBV Titer dynamics and immune function-related markers.

Any-grade AEs occurred in 76% vs 76% of the VT-EBV-N and control arms, with 10% vs 16% experiencing grade 3 or higher AEs. Serious AEs occurred in 19% vs 28% of each arm, with 1 patient in the control arm discontinuing treatment due to an AE. Adverse drug reactions (ADRs) occurred in 1 patient in the VT-EBV-N arm and included grade 2 ADR back pain and grade 1 ADR myalgia; no grade 3 ADRs were observed.

The most common AEs in the VT-EBV-N arm were COVID-19 infection (n = 5) and upper respiratory tract infection (n = 3). The most common AEs in the control arm were COVID-19 infection (n = 5), arthralgia (n = 4), sinusitis, increased aspartate aminotransferase, rhinorrhea, and peripheral neuropathy (each n = 3).

The investigators conducted this research to establish evidence-based standard therapy for ENKTL, which has shown sensitivity to radiotherapy and improved outcomes with non–anthracycline-based chemotherapy. VT-EBV-N was designed as an autologous EBV-specific cytotoxic T lymphocyte therapy to eliminate residual EBV-infected malignant cells.

A previous investigator-initiated study (KCT0001271) showed 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 after 4-year follow-up.² All remained alive at 4-year follow-up.

Yang noted that limitations included a need for additional subgroup analyses, biomarker and translational analyses, and patient-reported outcome data. He also acknowledged a lack of long-term follow-up data, which are necessary to confirm survival outcomes. Finally, he noted the need to extend the trial to include a more diverse study population, as well as further studies to clarify the mechanism of action for VT-EBV-N.

References

1. Jeon Y, Cho S-G, Yang D-H. VT-EBV-N as post-remission therapy significantly improves disease-free survival in EBV-positive extranodal NK/T-cell lymphoma: a randomized, double-blind phase 2 trial. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S245.
2. Cho S-G, Kim N, Sohn H-J, et al. Long-term outcome of extranodal NK/T cell lymphoma patients treated with postremission therapy using EBV LMP1 and LMP2a-specific CTLs. Mol Ther. 2015;23(8):1401-1409. doi:10.1038/mt.2015.91