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Current Treatment Options in Oncology Jan 2021While most patients with early-stage mycosis fungoides (MF) follow an indolent course, patients with advanced-stage MF/Sézary syndrome (SS) have a poor prognosis with a... (Review)
Review
While most patients with early-stage mycosis fungoides (MF) follow an indolent course, patients with advanced-stage MF/Sézary syndrome (SS) have a poor prognosis with a median survival of less than 5 years. Although there are a number of treatments currently available, achieving and maintaining a durable response remain challenging, especially in advanced-stage MF/SS. The choice of frontline therapy is dependent on the stage of disease. For early-stage MF, the treatment concept is to control skin lesions mainly by skin-directed therapies, such as topical therapies, phototherapies, and radiotherapies. For advanced-stage MF/SS, systemic treatments by biological or targeted therapies including bexarotene and interferon either alone or in combination are tried first, with more immunosuppressive chemotherapies being reserved for refractory or rapidly progressive disease. Recent improvements in biological or targeted therapies include brentuximab vedotin and mogamulizumab. When biopsy samples have 10% or more CD30-positive malignant cells, brentuximab vedotin, an anti-CD30 antibody conjugated to monomethyl auristin E, can be a desirable treatment option. For cases with blood involvement, mogamulizumab, an antibody binding to C-C chemokine receptor 4, is effective with high response rates. In the refractory setting, alemtuzumab, histone deacetylase inhibitors, pralatrexate, gemcitabine, and doxorubicin are considered as the treatment option. Because only allogeneic hematopoietic stem cell transplantation can offer a chance of cure with durable complete remission, advanced-stage patients with a markedly short life expectancy should be evaluated for eligibility. Given that there are few randomized controlled studies in the literature, it is necessary to investigate which therapy is preferable for each patient with MF/SS by comparative prospective trials.
Topics: Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Progression; Humans; Mycosis Fungoides; Neoplasm Grading; Neoplasm Staging; Prognosis; Sezary Syndrome; Skin Neoplasms; Treatment Outcome
PubMed: 33415447
DOI: 10.1007/s11864-020-00809-w -
Hematological Oncology Jun 2021Cutaneous T-cell lymphomas (CTCL) represent the majority of primary cutaneous lymphomas (CL). Mycosis fungoides (MF) and cutaneous CD30+ lymphoproliferative disorders... (Review)
Review
Cutaneous T-cell lymphomas (CTCL) represent the majority of primary cutaneous lymphomas (CL). Mycosis fungoides (MF) and cutaneous CD30+ lymphoproliferative disorders account for 80% of all CTCL. CTCL show overlapping histological features. Thus clinical-pathological correlation is of importance to achieve final diagnosis. MF shows a characteristic evolution with patches, plaques, and in a subset of patients (10%-20%) with tumors. Therapy is stage-adapted with skin-directed therapies such as UV-light therapies and corticosteroids in early disease stage (i.e., patch and limited plaque stage) and systemic therapies (retinoids, interferon, mono chemotherapy, targeted therapy) and/or radiation therapy (local or total skin beam electron) in advanced stages. Novel therapies include targeted therapy such as mogamulizumab (anti-CCR4) or brentuximab vedotin (anti-CD30) and histone deacetylase inhibitors. Considering the impact of targeted therapies, biomarkers such as CD30 are not only crucial for the diagnosis and correct classification of an individual lymphoma case, but also for therapy as they may represent therapeutic targets. In the recently revised WHO classification 2017 and the updated WHO-EORTC classification for CL 2018, primary cutaneous CD8+ acral T-cell lymphoma has been introduced as a new still provisional entity. It displays characteristic clinical, histological, and phenotypic features and exhibits an excellent prognosis. Rare, but aggressive CTCL include cutaneous primary cutaneous aggressive epidermotropic CD8-positive T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma, which present with rapid onset of necrotic or ulcerated plaques and tumors. As they have a poor prognosis, treatment includes multiagent chemotherapy and hematopoietic stem cell transplantation.
Topics: Humans; Mycosis Fungoides; Skin Neoplasms
PubMed: 34105822
DOI: 10.1002/hon.2850 -
European Journal of Cancer (Oxford,... Dec 2023On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated... (Review)
Review
On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.
Topics: Humans; Mycosis Fungoides; Sezary Syndrome; Consensus; Quality of Life; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms; Immunologic Factors
PubMed: 37890355
DOI: 10.1016/j.ejca.2023.113343 -
Blood Aug 2022The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical...
The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.
Topics: Clinical Trials as Topic; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Neoplasm Staging; Sezary Syndrome; Skin Neoplasms; United States
PubMed: 34758074
DOI: 10.1182/blood.2021012057 -
American Journal of Hematology Jan 2023Cutaneous T-cell lymphomas are a heterogenous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary...
DISEASE OVERVIEW
Cutaneous T-cell lymphomas are a heterogenous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS).
DIAGNOSIS
The diagnosis of MF or SS requires the integration of clinical and histopathologic data.
RISK-ADAPTED THERAPY
TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a "risk-adapted," multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin-directed therapies is preferred, as both disease-specific and overall survival for these patients is favorable. In contrast, patients with advanced-stage disease with significant nodal, visceral or the blood involvement are generally approached with systemic therapies, including biologic-response modifiers, histone deacetylase inhibitors, or antibody-based strategies, in an escalating fashion. In highly-selected patients, allogeneic stem-cell transplantation may be considered, as this may be curative in some patients.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Neoplasm Staging; Sezary Syndrome; Skin Neoplasms
PubMed: 36226409
DOI: 10.1002/ajh.26760 -
Journal of the National Comprehensive... May 2020Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL...
Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).
Topics: Guidelines as Topic; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Skin Neoplasms
PubMed: 32380458
DOI: 10.6004/jnccn.2020.0022 -
Journal of the American Academy of... Nov 2021Primary cutaneous T-cell lymphomas (CTCLs) are defined as lymphomas with a T-cell phenotype that present in the skin without evidence of systemic or extracutaneous... (Review)
Review
Primary cutaneous T-cell lymphomas (CTCLs) are defined as lymphomas with a T-cell phenotype that present in the skin without evidence of systemic or extracutaneous disease at initial presentation. CTCLs other than mycosis fungoides and Sézary syndrome (SS) account for approximately one third of CTCLs and encompass a heterogenous group of non-Hodgkin lymphomas, ranging from indolent lymphoproliferative disorders to aggressive malignancies with a poor prognosis. The spectrum of CTCLs continues to broaden as new provisional entities are classified. Given the morphologic and histologic overlap among CTCLs and other diagnoses, a thorough clinical history, physical evaluation, and clinicopathologic correlation are essential in the work up and diagnosis of these rare entities. This article will summarize the epidemiologic, clinical, pathologic, and diagnostic features of CTCLs other than mycosis fungoides and SS.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin; Skin Neoplasms
PubMed: 33940098
DOI: 10.1016/j.jaad.2021.04.080 -
JAMA Dermatology Nov 2023Since the increased use of dupilumab for atopic dermatitis (AD) in daily practice, several cases have been reported on the development of cutaneous T-cell lymphomas...
IMPORTANCE
Since the increased use of dupilumab for atopic dermatitis (AD) in daily practice, several cases have been reported on the development of cutaneous T-cell lymphomas (CTCL) and lymphoid infiltrates.
OBJECTIVE
To provide insight in the clinical and histopathologic features of patients with AD clinically suspected for CTCL during dupilumab treatment.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective observational case series included adult (≥18 years) patients with AD treated with dupilumab between October 2017 and July 2022 at the University Medical Center Utrecht in the Netherlands.
MAIN OUTCOMES AND MEASURES
Relevant patient, disease, and treatment characteristics were evaluated. Skin biopsies before, during, and after treatment were collected and reassessed.
RESULTS
Fourteen patients (54.5% male) with a median (IQR) age of 56 (36-66) years suspected for CTCL with deterioration of symptoms during dupilumab treatment were included. Of 14 patients, 3 were retrospectively diagnosed with preexistent mycosis fungoides (MF). Eleven patients with AD were eventually diagnosed with a lymphoid reaction (LR). These patients showed MF-like symptoms; however, histopathologic findings were different, and included sprinkled distribution of small hyperchromatic lymphocytes in the upper epidermal section, a dysregulated CD4:CD8 ratio, and CD30 overexpression, without loss of CD2/CD3/CD5. The median time to clinical worsening was 4.0 months (IQR, 1.4-10.0). Posttreatment biopsies showed complete clearance of the LR in all patients.
CONCLUSIONS AND RELEVANCE
This study found that dupilumab treatment can cause a reversible and benign LR, which mimics a CTCL, though has distinctive histopathologic features.
Topics: Adult; Humans; Male; Middle Aged; Aged; Female; Dermatitis, Atopic; Retrospective Studies; Skin Neoplasms; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous
PubMed: 37851456
DOI: 10.1001/jamadermatol.2023.3849 -
Journal of the American Academy of... May 2023
Topics: Humans; Sezary Syndrome; Mycosis Fungoides; Antibodies, Monoclonal, Humanized; Skin Neoplasms
PubMed: 36481378
DOI: 10.1016/j.jaad.2022.12.001 -
Lancet (London, England) Jun 2023Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell...
BACKGROUND
Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs.
METHODS
In this prospective, multicentre, matched controlled trial, conducted at 30 hospitals, participants with advanced CTCLs were allocated treatment: if they had an available compatible related donor they were assigned to allogeneic HSCT, or if not they were allocated to non-allogeneic HSCT therapy. Key inclusion criteria were participants aged 18-70 years, with advanced stage mycosis fungoides or Sézary syndrome, and at least one poor prognostic criteria. Participants were excluded if they were not in complete or partial remission of the disease. Propensity score 1:1 matching with replacement (ie, that each participant treated with HSCT was matched to the participant with the closest propensity score treated with non-HSCT therapy, even if they had already been matched) was used to handle confounding factors, with the balance of covariate distribution between HSCT and non-HSCT groups assessed using standardised mean differences. The primary endpoint was progression-free survival in the matched intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02520908), and is currently active but not recruiting.
FINDINGS
From June 1, 2016, to March 3, 2022, total of 99 participants were enrolled at 17 centres in France. Participants with a sibling or matched unrelated donor were assigned to allogeneic HSCT (HSCT group, n=55 [56%]) and participants without a donor were assigned to non-allogeneic HSCT treatment (non-HSCT group, n=44 [44%]). The median follow-up among survivors was 12·6 months (IQR 11·0-35·2). In the HSCT group, 51 participants (93%) were 1:1 matched to participants from the non-HSCT group. In the intention-to-treat analysis, median progression-free survival was significantly longer in the HSCT group (9·0 months [95% CI 6·6-30·5]) than in the non-HSCT group (3·0 months [2·0-6·3]), with a hazard ratio of 0·38 (95% CI 0·21-0·69; p<0·0001). In the per-protocol population, 40 participants (78%) in the HSCT group had 101 serious events and 29 participants (67%) in the non-HSCT group had 70 serious adverse events. The most common serious adverse event other than graft-versus-host disease in both groups was infections, occurring in 30 participants (59%) in the HSCT group and in 19 participants (44%) in the non-HSCT group.
INTERPRETATION
Allogeneic HSCT was associated with significantly longer progression-free survival in participants with advanced-stage CTCLs. These results indicate that allogeneic HSCT treatment should be made available to individuals with high-risk, advanced-stage mycosis fungoides or Sézary syndrome who achieve pre-transplant disease remission.
FUNDING
French Ministry of Health, National Cancer Institute, Programme Hospitalier de Recherche Clinique en Cancérologie.
Topics: Humans; Prospective Studies; Sezary Syndrome; Propensity Score; Lymphoma, T-Cell, Cutaneous; Transplantation, Homologous; Hematopoietic Stem Cell Transplantation; Mycosis Fungoides; Skin Neoplasms
PubMed: 37105210
DOI: 10.1016/S0140-6736(23)00329-X