ABSTRACT
Background: Sézary syndrome is an extremely rare and fatal cutaneous T-cell lymphoma (CTCL). Mogamulizumab, an anti-CCR4 monoclonal antibody, has recently been associated with increased progression-free survival in a randomized clinical trial in CTCL. We aimed to evaluate OS and prognostic factors in Sézary syndrome, including treatment with mogamulizumab, in a real-life setting. Methods: Data from patients with Sézary (ISCL/EORTC stage IV) and pre-Sézary (stage IIIB) syndrome diagnosed from 2000 to 2020 were obtained from 24 centers in Europe. Age, disease stage, plasma lactate dehydrogenases levels, blood eosinophilia at diagnosis, large-cell transformation and treatment received were analyzed in a multivariable Cox proportional hazard ratio model. This study has been registered in ClinicalTrials (SURPASSe01 study: NCT05206045). Findings: Three hundred and thirty-nine patients were included (58% men, median age at diagnosis of 70 years, Q1-Q3, 61-79): 33 pre-Sézary (9.7% of 339), 296 Sézary syndrome (87.3%), of whom 10 (2.9%) had large-cell transformation. One hundred and ten patients received mogamulizumab. Median follow-up was 58 months (95% confidence interval [CI], 53-68). OS was 46.5% (95% CI, 40.6%-53.3%) at 5 years. Multivariable analysis showed that age ≥ 80 versus <50 (HR: 4.9, 95% CI, 2.1-11.2, p = 0.001), and large-cell transformation (HR: 2.8, 95% CI, 1.6-5.1, p = 0.001) were independent and significant factors associated with reduced OS. Mogamulizumab treatment was significantly associated with decreased mortality (HR: 0.34, 95% CI, 0.15-0.80, p = 0.013). Interpretation: Treatment with mogamulizumab was significantly and independently associated with decreased mortality in Sézary syndrome. Funding: French Society of Dermatology, Swiss National Science Foundation (IZLIZ3_200253/1) and SKINTEGRITY.CH collaborative research program.
ABSTRACT
CD39, an ectoenzyme in the immunosuppressive CD39/CD73/adenosine pathway, known to promote solid tumour outgrowth and spreading, was investigated in both skin and blood compartments of cutaneous T cell lymphomas. CD39 was overexpressed by peripheral blood T-cells in Sezary syndrome and mycosis fungoides, and in skin-infiltrating lymphocytes of Sezary syndrome, mycosis fungoides, subcutaneous panniculitis-like T-cell lymphoma and primary cutaneous CD30-positive lymphoproliferation. Our study emphasizes the interest in using CD39/CD73/adenosine pathway blocking agents for cutaneous T cell lymphomas treatment.
Subject(s)
Antibodies, Monoclonal, Humanized , Lymphoma, T-Cell, Cutaneous , Receptors, CCR4 , Skin Neoplasms , Humans , Antibodies, Monoclonal, Humanized/adverse effects , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Receptors, CCR4/metabolism , Receptors, CCR4/antagonists & inhibitors , Lymphoma, T-Cell, Cutaneous/drug therapy , Lymphoma, T-Cell, Cutaneous/pathology , Male , Treatment Failure , Female , Aged , Middle AgedSubject(s)
Bronchiolitis Obliterans Syndrome , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Lymphoma, T-Cell, Cutaneous , Humans , Neoplasm Recurrence, Local , Nitriles , Lymphoma, T-Cell, Cutaneous/drug therapy , Graft vs Host Disease/drug therapy , Graft vs Host Disease/etiology , Retrospective Studies , Chronic DiseaseABSTRACT
Transmission of dermatophytes, especially Trichophyton mentagrophytes genotype VII, during sexual intercourse has been recently reported. We report 13 such cases in France. All patients were male; 12 were men who have sex with men. Our findings suggest sexual transmission of this pathogen within a specific population, men who have sex with men.