Abstract

Background: Novel Sézary syndrome (SS) biomarker genes identified previously through transcription profiling were examined for changes in expression after mogamulizumab treatment. Incorporating new biomarkers for measuring response to disease would improve clinical care. Objective: To assess novel SS biomarker and cytokine genes in patients treated with mogamulizumab with clinical response, blood response, and immunologic parameters. Methods: We performed a real-world case–control and case–case study analyzing the expression of SS biomarker genes in peripheral blood mononuclear cells (PBMCs) from six SS patients treated with mogamulizumab using qRT-PCR. Results: We demonstrated a reduced expression of SS biomarker genes in PBMCs of SS patients following mogamulizumab therapy. In our cohort, five of the SS biomarker genes (PLS3, TWIST1, KCNK1, DNM3 and TOX) showed statistically consistent high expression compared to normal PBMCs at baseline. After treatment with mogamalizumab, these five SS biomarkers showed significant correlations with skin response (p < 0.05) and three (TOX, TCRL3 and DNM3) with blood response (p < 0.05). A decrease in GATA3 expression correlated to an improvement in skin severity, and STAT4 inversely correlated to Sézary cell decrease (p < 0.05). Two cytokine genes, IL4 and IFNG, reflective of an immune response that is abnormal in SS, showed a trend to normalized expression with IL-4 decreasing and IFNG increasing after treatment. Limitations: This was a real-world study of patients who failed prior treatments, with a small sample size and variable timing between patient sample collection. Conclusions: Unique SS biomarker, cytokine and T cell transcription factor genes are valuable in assessing molecular and immune responses following treatment.

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