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Skin Therapy Letter Sep 2022Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US... (Review)
Review
Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US FDA in 1988 for the treatment of Sézary syndrome, a leukemic form of cutaneous T-cell lymphoma (CTCL). Although CTCL remains the only FDA-approved indication, ECP has since been used off-label for numerous other conditions, including graft-versus-host disease (GvHD), systemic sclerosis, autoimmune bullous dermatoses, Crohn's disease, and prevention of solid organ transplant rejection. In Canada, ECP is mainly used to treat CTCL, acute and chronic GvHD, and in some instances systemic sclerosis. Herein, we review the current concepts regarding ECP mechanism of action, treatment considerations and protocols, and efficacy.
Topics: Humans; Photopheresis; Graft vs Host Disease; Dermatology; Lymphoma, T-Cell, Cutaneous; Scleroderma, Systemic; Skin Neoplasms
PubMed: 36469458
DOI: No ID Found -
International Journal of Molecular... Nov 2021Mycosis fungoides (MF) and Sézary syndrome (SS), the most common types of cutaneous T-cell lymphoma (CTCL), are characterized by proliferation of mature CD4+ T-helper...
Mycosis fungoides (MF) and Sézary syndrome (SS), the most common types of cutaneous T-cell lymphoma (CTCL), are characterized by proliferation of mature CD4+ T-helper cells. Patients with advanced-stage MF and SS have poor prognosis, with 5-year survival rates of 52%. Although a variety of systemic therapies are currently available, there are no curative options for such patients except for stem cell transplantation, and thus the treatment of advanced MF and SS still remains challenging. Therefore, elucidation of the pathophysiology of MF/SS and development of medical treatments are desired. In this study, we focused on a molecule called OX40. We examined OX40 and OX40L expression and function using clinical samples of MF and SS and CTCL cell lines. OX40 and OX40L were co-expressed on tumor cells of MF and SS. OX40 and OX40L expression was increased and correlated with disease severity markers in MF/SS patients. Anti-OX40 antibody and anti-OX40L antibody suppressed the proliferation of CTCL cell lines both in vitro and in vivo. These results suggest that OX40-OX40L interactions could contribute to the proliferation of MF/SS tumor cells and that the disruption of OX40-OX40L interactions could become a new therapeutic strategy for the treatment of MF/SS.
Topics: Antibodies, Anti-Idiotypic; Antigens, Differentiation; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; OX40 Ligand; Sezary Syndrome
PubMed: 34830466
DOI: 10.3390/ijms222212576 -
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 -
Expert Review of Anticancer Therapy Sep 2021The most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS). In both MF and SS, complete responses to treatment are uncommon. Recent developments... (Review)
Review
INTRODUCTION
The most common types of CTCL are mycosis fungoides (MF) and Sézary syndrome (SS). In both MF and SS, complete responses to treatment are uncommon. Recent developments and understanding of the biology of MF/SS have led to novel agents which may offer prolonged responses with less toxicity compared to conventional chemotherapy approaches.
AREAS COVERED
In this review, we discuss the efficacy and safety of new nonchemotherapy treatment options including antibody agents, small molecule inhibitors, fusion proteins, and CAR T-cell therapy. We also reflect on older immunomodulatory treatments including retinoids and histone deacetylase inhibitors.
EXPERT OPINION
Patients with MF/SS who require systemic therapy often progress through multiple agents sequentially, thus the need for additional novel agents in the treatment armamentarium. Antibody-based therapies such as alemtuzumab are highly effective in the blood compartment of disease, while brentuximab vedotin has shown higher activity in skin and lymph nodes. Checkpoint inhibitors may play a role in treating MF/SS but may induce hyperprogression, and engineered T cells and bispecific antibodies recruiting immune effectors are being developed and may show promise in the future.
Topics: Disease Progression; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 33554707
DOI: 10.1080/14737140.2021.1882859 -
Bone Marrow Transplantation Jun 2021
Topics: Hematopoietic Stem Cell Transplantation; Humans; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 33526916
DOI: 10.1038/s41409-020-01150-4 -
Life (Basel, Switzerland) Feb 2024The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated... (Review)
Review
The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated pruritus is accepted. The prevailing Th2 profile in advanced CTCL underscores the significance of understanding IL-4/IL-13 expression dynamics from the early stages of disease, as a shift from Th1 to Th2 may explain CTCL progression. Targeted agents blocking key cytokines of type 2 immunity are established therapeutics in atopic disorders and have a promising therapeutic potential in CTCL, given their involvement in cutaneous symptoms and their contribution to the pathogenesis of disease. IL-4, IL-13, and IL-31 are implicated in pruritus, offering therapeutic targets with dupilumab, tralokinumab, lebrikizumab, and nemolizumab. This review analyzes current knowledge on the IL-4/IL-13 axis in mycosis fungoides and Sezary syndrome, the most common types of CTCL, examining existing literature on the pathogenetic implications with a focus on investigational treatments. Clinical trials and case reports are required to shed light on novel uses of medications in various diseases, and ongoing research into the role of IL-4/IL-13 axis blockers in CTCL therapy might not only improve the management of disease-related pruritus but also provide in-depth insights on the pathophysiologic mechanisms of CTCL.
PubMed: 38398754
DOI: 10.3390/life14020245 -
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 -
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 -
Cells Nov 2023In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in... (Review)
Review
In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.
Topics: Humans; Skin Neoplasms; Mycosis Fungoides; Brentuximab Vedotin; Sezary Syndrome; Antineoplastic Agents; Antibodies, Monoclonal
PubMed: 37998391
DOI: 10.3390/cells12222656 -
Clinical and Experimental Medicine Dec 2023Primary cutaneous T-cell lymphomas (CTCL), which include mycosis fungoides (MF) and Sézary syndrome (SS), are a group of lymphoproliferative disorders characterized by... (Review)
Review
Primary cutaneous T-cell lymphomas (CTCL), which include mycosis fungoides (MF) and Sézary syndrome (SS), are a group of lymphoproliferative disorders characterized by clonal accumulation of neoplastic T-lymphocytes in the skin. Severe pruritus, one of the most common and distressing symptoms in primary CTCL, can significantly impair emotional well-being, physical functioning, and interpersonal relationships, thus greatly reducing quality of life. Unfortunately, effectively managing pruritus remains challenging in CTCL patients as the underlying mechanisms are, as of yet, not fully understood. Previous studies investigating the mechanisms of itch in CTCL have identified several mediators and their corresponding antagonists used for treatment. However, a comprehensive overview of the mediators and receptors contributing to pruritus in primary CTCL is lacking in the current literature. Here, we summarize and review the mediators and receptors that may contribute to pruritus in primary CTCL to explore the mechanisms of CTCL pruritus and identify effective therapeutic targets using the PubMed and Web of Science databases. Studies were included if they described itch mediators and receptors in MF and SS. Overall, the available data suggest that proteases (mainly tryptase), and neuropeptides (particularly Substance P) may be of greatest interest. At the receptor level, cytokine receptors, MRGPRs, and TRP channels are most likely important. Future drug development efforts should concentrate on targeting these mediators and receptors for the treatment of CTCL pruritus.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Quality of Life; Skin Neoplasms; Mycosis Fungoides; Pruritus; Sezary Syndrome
PubMed: 37555911
DOI: 10.1007/s10238-023-01141-x