RESUMEN
Mogamulizumab is a first-in-class IgG1k monoclonal antibody that selectively targets the chemokine receptor type 4. The drug has received Food and Drug administration authorisation for mycosis fungoides and Sézary syndrome following failure of at least one previous course of systemic therapy and now is available in Europe. One of the most common treatment-related side effects observed has been the mogamulizumab-associated rash (MAR), which affects up to a quarter of patients and is the most frequent adverse event leading to drug discontinuation. The aim of this study is to perform a systematic review of the literature on patients diagnosed with MAR and other mogamulizumab-related cutaneous events to describe the clinical and histological characteristics, the management in clinical practice and to assess whether these events have prognostic implications. In total, 2073 records were initially identified through a literature search, 843 of which were duplicates. After screening for eligibility and inclusion criteria, 49 articles reporting mogamulizumab-associated cutaneous events were included. Totally, 1516 patients were retrieved, with a slight male prevalence as for the available data (639 males and 570 females, i.e. 52.9% vs. 47.1%). Regarding the reported clinicopathological findings of the cutaneous reactions, the five most common patterns were spongiotic/psoriasiform dermatitis (22%), eruptions characterized by the presence of papules and/or plaques (16.1%), cutaneous granulomatosis (11.4%), morbilliform or erythrodermic dermatitis (9.4%) and photodermatitis (7.1%). Our results highlight how the majority of the reported cutaneous adverse events on mogamulizumab are of mild-to-moderate entity and generally manageable in clinical practice, though prompt recognition is essential and case-by-case assessment should be recommended. Future research will need to focus on the MAR prognostic implications and to identify genomic and molecular markers for a more rapid and accurate diagnosis.
Asunto(s)
COVID-19/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Servicios Médicos de Urgencia/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , COVID-19/diagnóstico , COVID-19/virología , Interpretación Estadística de Datos , Dermatología/normas , Servicios Médicos de Urgencia/tendencias , Accesibilidad a los Servicios de Salud/tendencias , Humanos , Italia/epidemiología , Estudios Prospectivos , SARS-CoV-2/genéticaAsunto(s)
COVID-19 , Eritema Pernio , Vacunas contra la COVID-19 , Eritema Pernio/etiología , Humanos , ARN Mensajero , SARS-CoV-2Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Servicio de Urgencia en Hospital/organización & administración , Accesibilidad a los Servicios de Salud , Neumonía Viral/epidemiología , COVID-19 , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Femenino , Humanos , Italia/epidemiología , Masculino , Pandemias , Neumonía Viral/transmisión , Neumonía Viral/virología , SARS-CoV-2Asunto(s)
Carcinoma de Células de Merkel/diagnóstico , Anciano , Anciano de 80 o más Años , Carcinoma de Células de Merkel/diagnóstico por imagen , Carcinoma de Células de Merkel/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tasa de SupervivenciaAsunto(s)
Linfoma Cutáneo de Células T , Micosis Fungoide , Bexaroteno , Doxorrubicina , Humanos , Liposomas , Proyectos PilotoRESUMEN
Background: Gene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Patients and methods: Here, we applied the computational method CIBERSORT to generate a 1028-gene matrix incorporating signatures of 17 immune and stromal cytotypes. Then, we carried out a deconvolution on publicly available GEP data of 482 untreated DLBCLs to reveal associations between clinical outcomes and proportions of putative tumor-infiltrating cell types. Forty-five genes related to peculiar prognostic cytotypes were selected and their expression digitally quantified by NanoString technology on a validation set of 175 formalin-fixed, paraffin-embedded DLBCLs from two randomized trials. Data from an unsupervised clustering analysis were used to build a model of clustering assignment, whose prognostic value was also assessed on an independent cohort of 40 cases. All tissue samples consisted of pretreatment biopsies of advanced-stage DLBCLs treated by comparable R-CHOP/R-CHOP-like regimens. Results: In silico analysis demonstrated that higher proportion of myofibroblasts (MFs), dendritic cells, and CD4+ T cells correlated with better outcomes and the expression of genes in our panel is associated with a risk of overall and progression-free survival. In a multivariate Cox model, the microenvironment genes retained high prognostic performance independently of the cell-of-origin (COO), and integration of the two prognosticators (COO + TME) improved survival prediction in both validation set and independent cohort. Moreover, the major contribution of MF-related genes to the panel and Gene Set Enrichment Analysis suggested a strong influence of extracellular matrix determinants in DLBCL biology. Conclusions: Our study identified new prognostic categories of DLBCL, providing an easy-to-apply gene panel that powerfully predicts patients' survival. Moreover, owing to its relationship with specific stromal and immune components, the panel may acquire a predictive relevance in clinical trials exploring new drugs with known impact on TME.
Asunto(s)
Linfoma de Células B Grandes Difuso/mortalidad , Transcriptoma/genética , Microambiente Tumoral/genética , Adulto , Anciano , Algoritmos , Biopsia , Análisis por Conglomerados , Estudios de Cohortes , Biología Computacional , Conjuntos de Datos como Asunto , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Adhesión en Parafina , Valor Predictivo de las Pruebas , Pronóstico , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los Resultados , Análisis de Supervivencia , Adulto JovenAsunto(s)
Linfoma Cutáneo de Células T/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Cutáneas/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma Cutáneo de Células T/terapia , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/terapia , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/terapia , Tasa de SupervivenciaRESUMEN
BACKGROUND: Advanced-stage mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. PATIENTS AND METHODS: This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). RESULTS: Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. CONCLUSION: This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.
Asunto(s)
Micosis Fungoide/terapia , Síndrome de Sézary/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Brasil/epidemiología , Niño , Europa (Continente)/epidemiología , Femenino , Humanos , Japón/epidemiología , Masculino , Oncología Médica/métodos , Oncología Médica/estadística & datos numéricos , Persona de Mediana Edad , Micosis Fungoide/mortalidad , Micosis Fungoide/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Síndrome de Sézary/mortalidad , Síndrome de Sézary/patología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
A 65-year-old patient affected by mycosis fungoides (MF) stage IB achieved complete remission (CR) after a cycle of PUVA phototherapy. The U.S. Cutaneous Lymphoma Consortium (USCLC) guidelines suggest that the patient should be kept in the maintenance phase, defined as a 'period of gradual decrease of frequency of UVL [ultraviolet light] while in clinical remission before discontinuation of phototherapy' by slowly tapering the number of psoralen-ultraviolet A (PUVA) applications over time up to clinical relapse. The USCLC guidelines also suggest a standardized schedule for the maintenance phase. Alternatively, the patient could end PUVA therapy and go straight to follow-up. The aim of this critically appraised topic (CAT) was to determine if a maintenance phase gives a significant benefit in terms of relapse rate (RR) and RFI in patients affected by early-stage MF who had achieved CR under PUVA phototherapy. Embase, PubMed and TRIP databases were searched for 'mycosis fungoides' AND [('photochemotherapy' OR 'puva') OR 'psoralen'] in June 2016. Three articles matched our inclusion criteria and are discussed in this CAT. In this field of research the literature is poor and the reported level of evidence is low. Only one of the studies was conducted prospectively, and none were randomized. No significant difference in terms of reduction in relapse rate or increase in RFI in patients who underwent a PUVA maintenance phase emerged when compared with those who went for simple follow-up. Further randomized clinical trials (RCTs) are required in order to evaluate maintenance phase vs. no treatment before it can be favoured as the standard protocol of treatment in early-stage MF. At the time of writing this paper, we report an ongoing Austrian multicentre RCT (Clinical Trial.gov identifier: NCT01686594) that will hopefully give useful results in this topic.