RESUMO
Kimura disease (KD) is a rare, chronic angiolymphoproliferative inflammatory disease appearing to be mostly restricted to the skin and soft tissue. Cutaneous involvement of KD includes head and/or neck nodules showing suggestive histological features, frequently associated with an atopic dermatitis-like or prurigo-like presentation. KD is challenging to treat, with high rate of recurrence using current therapeutic strategies. Evidence for involvement of a T-helper type 2 (Th2) immune response in KD pathogenesis has been found in previous studies. Consequently, this study aimed to determine the efficacy and safety of dupilumab, a human monoclonal antibody that inhibits signalling of key Th2 cytokines, interleukin (IL)-4 and IL-13, within a single-centre cohort of patients with cutaneous KD. Two adults with a diagnosis of refractory (failure of at least one treatment line) cutaneous-restricted KD based on clinical, biological, histological, molecular and imaging findings received dupilumab for KD, and showed dramatic response with a good safety profile.
Assuntos
Anticorpos Monoclonais Humanizados , Doença de Kimura , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Adulto , Doença de Kimura/tratamento farmacológico , Doença de Kimura/patologia , Pessoa de Meia-Idade , Feminino , Resultado do Tratamento , Interleucina-4 , Interleucina-13/antagonistas & inibidoresAssuntos
Anticorpos Monoclonais Humanizados , Complexo CD3 , Síndrome Hipereosinofílica , Receptores CCR4 , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/patologia , Receptores CCR4/antagonistas & inibidores , Receptores CCR4/metabolismo , Masculino , Pessoa de Meia-Idade , Feminino , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Resultado do Tratamento , Idoso , Antígenos CD4/metabolismoAssuntos
Anticorpos Monoclonais Humanizados , Linfoma Cutâneo de Células T , Receptores CCR4 , Neoplasias Cutâneas , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Receptores CCR4/metabolismo , Receptores CCR4/antagonistas & inibidores , Linfoma Cutâneo de Células T/tratamento farmacológico , Linfoma Cutâneo de Células T/patologia , Masculino , Falha de Tratamento , Feminino , Idoso , Pessoa de Meia-IdadeAssuntos
Anticorpos Monoclonais Humanizados , Progressão da Doença , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Síndrome de Sézary/tratamento farmacológico , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Feminino , Idoso , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Pessoa de Meia-Idade , Suspensão de Tratamento , Idoso de 80 Anos ou mais , AdultoAssuntos
Doença Enxerto-Hospedeiro , Humanos , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/etiologia , Masculino , Doenças Musculares/etiologia , Doenças Musculares/patologia , Doenças Musculares/imunologia , Doença Crônica , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pessoa de Meia-Idade , Feminino , Adulto , Síndrome de Bronquiolite ObliteranteRESUMO
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.
RESUMO
Cutaneous T-cell lymphomas (CTCL) are a diverse group of malignant blood disorders characterized by initial skin infiltration, and sometimes, tumor spreading to lymph nodes, blood, and viscera. Mycosis fungoides is the most common form. Sézary syndrome is a distinctive form of CTCL marked by a significant presence of circulating tumor cells in peripheral blood. These diseases are characterized by the plasticity and heterogeneity of the tumor cells in the different tissue compartments, and a difficulty in identifying these tumor cells for diagnostic purposes and therapeutic monitoring. Progress has been made in the understanding of the pathophysiology of these diseases in recent years, and we provide here a review of these advancements.
Assuntos
Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Humanos , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/imunologia , Linfoma Cutâneo de Células T/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/diagnóstico , França , Síndrome de Sézary/patologia , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/imunologia , Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Micose Fungoide/imunologia , Encaminhamento e ConsultaRESUMO
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.