Celia Mundt, BA: No financial relationships to disclose
Introduction/Rationale: Cutaneous T cell lymphoma (CTCL) is a rare non-Hodgkin lymphoma marked by malignant T cell infiltration of the skin, which is often accompanied by chronic inflammation and progressive immunosuppression. While most human CTCL cases express CD4, a subset present with aggressive CD8+ lymphoma. Recent studies suggest that epitheliotropic lymphoma (EL) that develops spontaneously in pet dogs closely resembles CD8+ CTCL subtypes, indicating its potential value as a translational model for studying novel therapies related to CTCL. The objective of this study was to evaluate the efficacy and safety of combined PD1 and XPO1 inhibition in pet dog CTCL, and to identify differentially expressed immune genes linked to treatment response and prognosis.
Methods: Six client-owned pet dogs with biopsy confirmed CTCL were enrolled in a non-randomized clinical trial of gilvetmab (canine anti-PD1) and verdinexor (XPO1 inhibitor). Over sixteen weeks, skin biopsies and tape strips were collected from each canine at weeks 0, 8 and 16 to assess longitudinal gene changes. Clinical evaluations tracked progression-free survival (PFS) and overall survival time (OST). Differential gene expression was compared between healthy controls and short vs long term PFS using microarray technology.
Results: Combination therapy achieved a 50% overall response rate, with a median OST of 480 days and n=4 pets alive at study end. Pet dogs with a longer PFS demonstrated distinct immune gene signatures compared to shorter PFS: SAA1 and CXCL13 were upregulated in short-term PFS, while C1R and CCL21 were elevated in longer PFS.
Conclusion: PD1 and XPO1 inhibition is a feasible and potentially immunoprotective strategy in CD8+ CTCL. Transcriptomic findings reveal immune genes linked to poor prognosis, as well as candidate biomarkers associated with improved outcomes. Given the parallels between pet dog and human CD8+ CTCL, this model offers promising insights for advancing comparative oncology and developing more effective immunotherapies.
