Background

Sézary syndrome is a severe primary cutaneous lymphoma with blood involvement and a particularly poor prognosis. Definitive cure is exceptional and relapses are frequently observed to classical treatments. With the emergence of new, more effective treatments the measurement of the blood burden of Sézary syndrome gains on importance. Blood staging criteria were defined based on lymphocyte epitope losses such as CD7 and CD26. Our group described earlier the validity of KIR3DL2 expression in the initial diagnosis of Sézary syndrome (Roelens et al. 2019). Blood response criteria to treatment were introduced and recently refined by the European Organisation for Research and Treatment of Cancer Cutaneous Lymphoma Task Force. However, we lack on evidence on the sensitivity to change of established and more recent biomarkers.

Methods

Aim of this study was to describe the sensitivity to change of KIR3DL2 on the blood burden of Sézary syndrome in real world setting. A monocentric retrospective cohort of patients with Sézary syndrome were included in this explorative study and their flow cytometry data were analyzed at repeated measurement points. The patients were divided into groups by the treatment they received and subgroup analysis was performed. We compared to the gold standard parameters, CD4/CD8, CD4+CD7- and CD4+CD26- levels with KIR3DL2 expressions, ratios and related parameters.

Results

Between 2015 and 2020 altogether 73 patients received an ambulant treatment (e. g. bexarotene, methotrexate or interferon), 55 patients received ECP-based therapy, 52 patients monochemotherapy and 79 patients monoclonal antibodies. The longitudinal validity of the above mentioned biomarkers were analyzed within nine treatment groups, all including at least 10 patients. The CD4+CD26- and CD4+KIR3DL2+ lymphocytes seemed to reflect the blood involvement most precisely. These two parameters showed high correlations in each treatment group, suggesting high validity as compared to e. g. CD4+CD7-. Absolute expression of KIR3DL2 seemed to have the best validity in patients having lymphopenia.

Conclusion

These results demonstrate the longitudinal validity of the currently used cytometry based biomarkers in Sézary syndrome in different treatment groups, highlighting the usefulness of KIR3DL2 especially in lymphopenic patients. Furthermore, these results provide also evidence on the efficacy of methotrexate, bexarotene, bexarotene and ECP, romidepsine, gemcitabine, doxorubicine, etoposide and ifosfamide, mogamulizumab and lacutamab in the treatment of Sézary syndrome.



Figures: CD4/CD8 ratio and absolute cell counts using the different biomarkers in patients receiving bexarotene monotherapy. The bold black line displays the average.