Discussion
tumor, EBV-infected tumor, EBVTo gain, lymphoma, multiple lymphoma, EBV-positivity
LYMPHOMA, TUMOR
EBVEBV lytic cycle activation with HDACi in combination with GCV as an effective approach to eliminate EBV-infected tumor cells has a strong mechanistic rationale and has been validated preclinically in multiple studies.Although all patients enrolled in this study had EBVTo gain insight into the patterns and range of tumor cell EBV-positivity in this heterogeneous population, we performed postenrollment centralized EBER-ISH staining on all available tumor specimens (EBV “viral loads” measured in plasma or whole blood at baseline or longitudinally are robust and clinically applicable prognostic biomarkers in some EBVThe patient cohort enrolled in this phase 1b/2 study was very heterogeneous. While safety and tolerability were good, and there was a clear efficacy signal, any conclusion about which subset of EBVThis study has limitations. First, the study design did not allow for a formal assessment of the relative contributions of Nstat and VGCV to the observed antitumor responses. Although a large body of preclinical data supports the concept that the combination of Nstat and VGCV is necessary to achieve the “kick and kill” effect in EBVIn conclusion, targeted therapy with Nstat in combination with VGCV is a promising novel approach with the potential to fill an important gap in the complex treatment algorithm for lymphoma by addressing a recently recognized and untapped tumor-specific vulnerability shared by multiple lymphoma subtypes. Further investigation of Nstat-VGCV in the ongoing phase 2 NAVAL-1 study will further highlight the prevalence and unmet needs of patients with EBVConflict-of-interest disclosure: B.H. reports consultancy fees from Viracta Therapeutics. R.B. reports participation in scientific advisory boards for Viracta Therapeutics and Atara; research funding from The current affiliation for D.V.F. is Oryzon Genomics, Boston, MA.