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Frontiers in Immunology 2023Mycosis fungoides (MF) and Sézary syndrome (SS) are forms of cutaneous T cell lymphoma (CTCL) that pose significant challenges in their clinical management,... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are forms of cutaneous T cell lymphoma (CTCL) that pose significant challenges in their clinical management, particularly in refractory and advanced-stage disease. With the emergence of novel therapeutic modalities however, there are increasing opportunities to exploit the current understanding of pathophysiologic mechanisms of MF/SS for treatment. This review summarizes recent advances in the treatment of MF/SS, with a focus on monoclonal antibodies, immunotherapies, and Janus kinase (JAK) inhibitors, including ongoing clinical trials.
Topics: Humans; Sezary Syndrome; Antibodies, Monoclonal; Janus Kinase Inhibitors; Skin Neoplasms; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Immunotherapy
PubMed: 38022633
DOI: 10.3389/fimmu.2023.1291259 -
Frontiers in Immunology 2023Mycoses fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas that are often challenging to manage given the absence of reliably curative therapies, at... (Review)
Review
Mycoses fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas that are often challenging to manage given the absence of reliably curative therapies, at times high symptom burden with significant detriment to quality of life, and need for ongoing treatment for disease and symptom control. Recent developments in skin-directed treatments include optimizing the use of existing topical therapies, the introduction of known dermatological agents and treatment modalities for the specific treatment of MF/SS (such as mechlorethamine gel, calcineurin inhibitor creams, and photodynamic therapy), and novel local and topical agents. For advanced disease, dedicated clinical trials have translated to exciting progress, leading to the approval of brentuximab vedotin (2017) and mogamulizumab (2018) for relapsed MF/SS. Additional studies of other active systemic agents, including various cellular therapies, represent further attempts to add to the therapeutic armamentarium in treating MF/SS. In this review, we highlight these recent advancements, ranging from optimization of skin-directed therapies to the introduction of novel systemic agents. We focus on therapies approved in the preceding five years or under investigation in advanced-phase clinical trials.
Topics: Humans; Sezary Syndrome; Quality of Life; Skin Neoplasms; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Mycoses
PubMed: 37868986
DOI: 10.3389/fimmu.2023.1284045 -
Pathogens (Basel, Switzerland) Aug 2022In recent years, numerous studies have shown a significant role of the skin microbiome in the development and exacerbation of skin diseases. Cutaneous T-cell lymphomas... (Review)
Review
In recent years, numerous studies have shown a significant role of the skin microbiome in the development and exacerbation of skin diseases. Cutaneous T-cell lymphomas (CTCL) are a group of malignancies primary involving skin, with unclear pathogenesis and etiology. As external triggers appear to contribute to chronic skin inflammation and the malignant transformation of T-cells, some microorganisms or dysbiosis may be involved in these processes. Recently, studies analyzing the skin microbiome composition and diversity have been willingly conducted in CTCL patients. In this review, we summarize currently available data on the skin microbiome in CTLC. We refer to a healthy skin microbiome and the contribution of microorganisms in the pathogenesis and progression of other skin diseases, focusing on atopic dermatitis and its similarities to CTCL. Moreover, we present information about the possible role of identified microorganisms in CTCL development and progression. Additionally, we summarize information about the involvement of in CTCL pathogenesis. This article also presents therapeutic options used in CTCL and discusses how they may influence the microbiome.
PubMed: 36015055
DOI: 10.3390/pathogens11080935 -
Mediterranean Journal of Hematology and... 2022Cutaneous T-cell lymphomas are a heterogeneous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary... (Review)
Review
Cutaneous T-cell lymphomas are a heterogeneous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). Mycosis fungoides (MF) is usually associated with an indolent clinical course and intermittent, stable, or slow progression of the lesions. Extracutaneous involvement (lymph nodes, blood, or less commonly other organs) or large cell transformation (LCT) may be seen in advanced-stage disease. Sezary syndrome (SS) is a rare leukemic subtype of CTCL characterized by significant blood involvement, erythroderma, and often lymphadenopathy. Although the early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary to treat advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as vorinostat, brentuximab vedotin, and mogamulizumab. This review aims to discuss the diagnosis and management of advanced-stages MF and SS.
PubMed: 35444765
DOI: 10.4084/MJHID.2022.029 -
The British Journal of Dermatology Jul 2021Mycosis fungoides (MF) and Sézary syndrome (SS) are the best-studied subtypes of cutaneous T-cell lymphoma. The level of blood tumour burden in patients is important... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are the best-studied subtypes of cutaneous T-cell lymphoma. The level of blood tumour burden in patients is important for diagnosis, disease staging, prognosis and management, as well as assessing treatment response. Until recently, the assessment of blood involvement was made using manual counts of morphologically atypical T cells (Sézary cells), but this approach may be subjective, and is affected by interobserver variability. Objective and consistent approaches to accurately quantifying blood involvement are required to ensure appropriate stage-related management of patients and to improve our understanding of the prognostic implications of blood tumour burden in these diseases. While assessment of blood involvement is common in SS and advanced-stage MF, an improved understanding of the implications of blood involvement at early disease stages could help identify patients more likely to progress to late-stage disease, and hence guide treatment decisions and frequency of follow-up assessment, ultimately improving patient outcomes. This concise review discusses the development of flow cytometry-based classifications for assessing blood involvement in MF and SS, and summarizes current recommendations for blood classification and assessment of blood response to treatment.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Neoplasm Staging; Sezary Syndrome; Skin Neoplasms; Tumor Burden
PubMed: 33155285
DOI: 10.1111/bjd.19669 -
Cells Aug 2020Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma (CTCL) with poor prognosis, is characterized by the clinical hallmarks of circulating malignant T cells,... (Review)
Review
Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma (CTCL) with poor prognosis, is characterized by the clinical hallmarks of circulating malignant T cells, erythroderma and lymphadenopathy. However, highly variable clinical skin manifestations and similarities with benign mimickers can lead to significant diagnostic delay and inappropriate therapy that can lead to disease progression and mortality. SS has been the focus of numerous transcriptomic-profiling studies to identify sensitive and specific diagnostic and prognostic biomarkers. Benign inflammatory disease controls (e.g., psoriasis, atopic dermatitis) have served to identify chronic inflammatory phenotypes in gene expression profiles, but provide limited insight into the lymphoproliferative and oncogenic roles of abnormal gene expression in SS. This perspective was recently clarified by a transcriptome meta-analysis comparing SS and lymphocytic-variant hypereosinophilic syndrome, a benign yet often clonal T-cell lymphoproliferation, with clinical features similar to SS. Here we review the rationale for selecting lymphocytic-variant hypereosinophilic syndrome (L-HES) as a disease control for SS, and discuss differentially expressed genes that may distinguish benign from malignant lymphoproliferative phenotypes, including additional context from prior gene expression studies to improve understanding of genes important in SS.
Topics: Biomarkers; Gene Expression; Humans; Hypereosinophilic Syndrome; Sezary Syndrome
PubMed: 32872487
DOI: 10.3390/cells9091992 -
Journal of the European Academy of... Feb 2023Cutaneous T-cell lymphomas (CTCL) are rare types of non-Hodgkin lymphoma, which present in skin. Mycosis fungoides (MF) and Sézary syndrome (SS) are subtypes which make... (Clinical Trial)
Clinical Trial
BACKGROUND
Cutaneous T-cell lymphomas (CTCL) are rare types of non-Hodgkin lymphoma, which present in skin. Mycosis fungoides (MF) and Sézary syndrome (SS) are subtypes which make up two-thirds of all CTCL cases. The phase 3 MAVORIC study (NCT01728805) compared mogamulizumab to vorinostat in MF and SS patients, with post hoc data showing a trend for higher efficacy in mogamulizumab-treated patients as baseline blood tumour burden increases.
OBJECTIVES
The aim of this study was to use updated post hoc analyses in order to examine the efficacy of mogamulizumab and vorinostat in MF patients when stratified by baseline blood involvement and to determine what factors affect time-to-global and time-to-skin response to inform clinical follow-up.
METHODS
Post hoc analyses were carried out using data from MAVORIC. Overall response rate (ORR), progression-free survival (PFS) and time-to-next-treatment (TTNT) data were used to assess efficacy in patients with MF. Time-to-global response (TTR) was examined by disease subtype, by blood involvement in MF patients, and time-to-skin response was examined by blood involvement in MF patients.
RESULTS
Numerically superior results were seen for ORR, PFS and TTNT in mogamulizumab-treated patients with MF compared with vorinostat, with a trend for outcomes improving with increasing baseline blood class. Statistically significant results for mogamulizumab compared with vorinostat were seen for MF B1 pts for PFS (8.43 vs. 2.83 months, p = 0.003) and TTNT (11.9 vs. 3.13 months, p = 0.002), and for MF B2 pts for ORR (46.2 vs. 9.1 months, p = 0.033).
CONCLUSIONS
In mogamulizumab-treated MF patients, ORR and PFS were seen to improve with increasing blood involvement, which led to improved TTNT. TTR was more predictable for mogamulizumab-treated MF patients with blood involvement, and skin response may take longer than previously reported in some patients.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms; Vorinostat
PubMed: 35993803
DOI: 10.1111/jdv.18549 -
FEBS Open Bio Jul 2023Cutaneous T-cell lymphoma (CTCL) encompasses two main subtypes: mycosis fungoides and Sezary syndrome. Global response rates for the systemic treatment of mycosis...
Cutaneous T-cell lymphoma (CTCL) encompasses two main subtypes: mycosis fungoides and Sezary syndrome. Global response rates for the systemic treatment of mycosis fungoides and Sezary syndrome are approximately 30%, and none of these treatments are thought to be curative. C-C chemokine receptor type 4 (CCR4) and CD25 are encouraging targets for the treatment of CTCL and are individually targeted by mogamulizumab and denileukin diftitox, respectively. We developed a novel CCR4-IL2 bispecific immunotoxin (CCR4-IL2 IT) targeting both CCR4 and CD25. CCR4-IL2 IT demonstrated superior efficacy against CCR4 CD25 CD30 CTCL in an immunodeficient NSG mouse tumor model. Investigative New Drug-enabling studies of CCR4-IL2 IT are ongoing, including Good Manufacturing Practice production and toxicology studies. In this study, we compared the in vivo efficacy of CCR4-IL2 IT versus the US Food and Drug Administration-approved drug, brentuximab, using an immunodeficient mouse CTCL model. We demonstrated that CCR4-IL2 IT was significantly more effective in prolonging survival than brentuximab, and combination treatment of CCR4-IL2 IT and brentuximab was more effective than brentuximab or CCR4-IL2 IT alone in an immunodeficient NSG mouse CTCL model. Thus, CCR4-IL2 IT is a promising novel therapeutic drug candidate for CTCL treatment.
Topics: United States; Animals; Mice; Immunotoxins; Sezary Syndrome; Interleukin-2; Skin Neoplasms; Lymphoma, T-Cell, Cutaneous; Antineoplastic Agents; Mycosis Fungoides; Antibodies, Monoclonal
PubMed: 37157185
DOI: 10.1002/2211-5463.13625 -
Best Practice & Research. Clinical... Sep 2019Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas.... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas. Diagnosis requires correlation of clinical, histologic, and molecular features. A multitude of factors have been linked to the aetiopathogenesis, however, none have been definitively proven. Erythrodermic MF (E-MF) and SS share overlapping clinical features, such as erythroderma, but are differentiated on the degree of malignant blood involvement. While related, they are considered to be two distinct entities originating from different memory T cell subsets. Differential expression of PD-1 and KIR3DL2 may represent a tool for distinguishing MF and SS, as well as a means of monitoring treatment response. Treatment of E-MF/SS is guided by disease burden, patients' ages and comorbidities, and effect on quality of life. Current treatment options include biologic, targeted, immunologic, and investigational therapies that can provide long term response with minimal side effects. Currently, allogeneic stem cell transplantation is the only potential curative treatment.
Topics: Humans; Immunologic Memory; Mycosis Fungoides; Neoplasm Proteins; Programmed Cell Death 1 Receptor; Receptors, KIR3DL2; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 31585624
DOI: 10.1016/j.beha.2019.06.004 -
Dermatology and Therapy Jan 2022The CCR4-directed monoclonal antibody mogamulizumab has been shown to significantly improve progression-free survival and overall response rate compared with vorinostat... (Review)
Review
The CCR4-directed monoclonal antibody mogamulizumab has been shown to significantly improve progression-free survival and overall response rate compared with vorinostat in adults with relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS). One of the most common adverse events seen with mogamulizumab in MF/SS patients is rash. Because of the protean nature of MF/SS and the variable clinical and histopathological features of mogamulizumab-associated rash, healthcare providers may have difficulty distinguishing rash from disease, and may not be aware of appropriate treatment strategies for this generally manageable adverse event. The objective of this report was to combine results from published literature with experiences and recommendations from multiple investigators and institutions into clinical best practice recommendations to assist healthcare providers in identifying and managing mogamulizumab-associated rash. Optimal management, which includes biopsy confirmation and steroid treatment, requires a multidisciplinary approach among oncology, dermatology, and pathology practitioners. INFOGRAPHIC.
PubMed: 34816383
DOI: 10.1007/s13555-021-00624-7