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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 -
Revue Medicale Suisse Mar 2022The two main subtypes of primary cutaneous T-cell lymphomas include the most frequent, mycosis fungoides (MF), and the rare leukemic variant, Sézary syndrome (SS). MF...
The two main subtypes of primary cutaneous T-cell lymphomas include the most frequent, mycosis fungoides (MF), and the rare leukemic variant, Sézary syndrome (SS). MF presents as cutaneous patches and can progress to plaques, tumors and erythroderma. SS is characterized by the presence of erythroderma, generalized lymphadenopathy and clonal T cells in the peripheral blood, consistent with a poorer prognosis. Histologically, early CTCL lesions are sometimes indistinguishable from more common inflammatory skin diseases and a clinico-pathological correlation is essential for an accurate diagnosis. Except for allogenic stem-cell transplantation, therapy is generally palliative and aims to improve patient quality of life.
Topics: Humans; Mycosis Fungoides; Quality of Life; Sezary Syndrome; Skin Neoplasms; T-Lymphocytes
PubMed: 35353453
DOI: 10.53738/REVMED.2022.18.775.578 -
Journal of the European Academy of... Dec 2021Cutaneous T-cell Lymphoma's (CTCL) are a rare, heterogeneous group of T-cell lymphomas that primarily manifest in the skin. Mycosis fungoides (MF) and Sézary syndrome... (Review)
Review
Cutaneous T-cell Lymphoma's (CTCL) are a rare, heterogeneous group of T-cell lymphomas that primarily manifest in the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) are considered the classic types of CTCL. The diverse manifestation of CTCL results in a wide range of symptoms with a possible mild to severe impact on Quality of Life (QoL) depending on the disease stage. Previous studies on QoL in CTCL patients report diverse patient populations and use many different QoL instruments. In the current literature, a clear overview on the influence of the different stages of disease (early MF, late-stage MF/SS or total group) on the QoL is lacking. Therefore, a systematic search of the literature was conducted using the PubMed, Embase, PsycINFO and Web of Science databases. Studies were included if they described QoL in patients with MF and SS retrieved by standardized instruments or qualitative interviews. In total, 24 studies were included using 18 different questionnaires to report on dermatology-specific, cancer-specific and generic QoL. The effect on QoL was found to be greater in patients with late-stage disease as compared to early stage disease, with significant impairments on functional, emotional and physical domains. Nonetheless, even in patients with limited disease, QoL was mildly to moderately affected. Overall, pruritus was the most frequent reported and most bothersome symptom. Significant influence of the disease on daily life activities were found, not only in patients but also on caregivers and family. This broad, structured overview on QoL in MF and SS patients underlines the influence of disease stage on QoL, and therefore, recommends future studies to distinguish between disease stages when reporting results. Furthermore, this overview can inform clinicians in clinical practice by creating awareness of QoL deficits according to disease stage.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Quality of Life; Sezary Syndrome; Skin Neoplasms
PubMed: 34331819
DOI: 10.1111/jdv.17570 -
Bone Marrow Transplantation Jan 2024Allogeneic hematopoietic stem cell transplant (allo-HSCT) has been noted to be a potential curative treatment in cases of advanced-stage mycosis fungoides (MF) or Sezary... (Meta-Analysis)
Meta-Analysis
Allogeneic hematopoietic stem cell transplant (allo-HSCT) has been noted to be a potential curative treatment in cases of advanced-stage mycosis fungoides (MF) or Sezary syndrome (SS). To assess outcomes of allo-HSCT for MF/SS we performed a systematic review and meta-analysis including 15 manuscripts and 557 patients, published from 2010-2023. Meta-analysis revealed 1-year and 3+year overall survival (OS) of 51% (95% CI 39-64%) and 40% (32-49%). Progression-free survival at 1 year and 3+years were 42% (31-53%) and 33% (25-42%). Non-relapse mortality was 18% (13-23%). Relapse occurred in of 47% (40-53%) with a median time to relapse of 7.9 months (range 1.6-24 months). Rates of acute and chronic graft-versus-host disease (GVHD) were 45% (35-55%) and 40% (33-48%). Reduced-intensity conditioning (RIC) was associated with superior OS compared to myeloablative conditioning (MAC) (58% vs. 30%, p < 0.001). Of patients with relapse after allo-HSCT, 46% treated with donor lymphocyte infusion (DLI) achieved complete remission. These data support use of allo-HSCT for treatment of advanced-stage MF/SS and suggest superiority of RIC over MAC. Rates of GVHD were comparable to allo-HSCT in general. The improved OS for RIC and high rate of CR with DLI underscore the importance of the graft-versus-lymphoma effect in allo-HSCT for MF/SS.
Topics: Humans; Sezary Syndrome; Transplantation, Homologous; Neoplasm Recurrence, Local; Mycosis Fungoides; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Graft vs Host Disease; Skin Neoplasms; Recurrence; Retrospective Studies
PubMed: 37853164
DOI: 10.1038/s41409-023-02122-0 -
PharmacoEconomics May 2022The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Kyowa Kirin) of mogamulizumab (Poteligeo), as part of the single technology... (Review)
Review
The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Kyowa Kirin) of mogamulizumab (Poteligeo), as part of the single technology appraisal process, to submit evidence for its clinical and cost-effectiveness for previously treated mycosis fungoides (MF) and Sézary syndrome (SS). Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre, was commissioned to act as the independent evidence review group (ERG). This paper summarises the company submission (CS), presents the ERG's critical review of the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations and describes the development of the NICE guidance by the Appraisal Committee. Based on a systematic literature review, one randomised controlled trial, MAVORIC, was identified showing favourable results in patients with MF and SS. However, MAVORIC compared mogamulizumab to vorinostat, which is not standard care in the NHS, and there is uncertainty due to the study design, specifically crossover of patients. Based on a "naïve comparison of results from the vorinostat arm of the MAVORIC study and the physician's choice arm (methotrexate or bexarotene i.e. United Kingdom [UK] standard treatments) of the ALCANZA study as well as comparison to Phase II bexarotene data", the company considered vorinostat to be "a reasonable proxy for current standard of care in the NHS". The ERG considered, based on the limited data available, that the comparability of vorinostat (MAVORIC) and physician's choice (ALCANZA) could not be established. In response to the Appraisal Consultation Document, the company provided an unanchored matched adjusted indirect comparison (MAIC) of mogamulizumab with UK standard care by analysing Hospital Episode Statistics (HES) data. However, given the high risk of bias of an unanchored MAIC, these results needed to be regarded with a considerable degree of caution. The economic analysis suffered from uncertainty because there was no trial evidence on the comparator in the England and Wales National Health Service (NHS), and it was unclear to what extent the trial (MAVORIC) comparator (vorinostat) was comparable to standard care, referred to as established clinical management (ECM) in the NHS. The evidence for overall survival had not reached maturity and was confounded by treatment switching, for which different crossover adjustment methods produced large variations in life years. Caregiver utilities were applied in the analysis, but there was a lack of guidance on their application and whether these were indicated in this appraisal. After consultation, the company updated the economic analysis with the MAIC. Incremental cost-effectiveness ratios comparing mogamulizumab against ECM were (depending on whether the HES or MAVORIC comparison were used) £31,030 or £32,634 per quality-adjusted life years (QALYs) gained according to the company's base case and £38,274 or £80,555 per QALY gained according to the ERG's base case. NICE did not recommend mogamulizumab for treating MF or SS in adults who have had at least one previous systemic treatment. This decision was subsequently appealed, and an appeal decision has been reached.
Topics: Adult; Antibodies, Monoclonal, Humanized; Bexarotene; Cost-Benefit Analysis; Humans; Mycosis Fungoides; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Sezary Syndrome; Skin Neoplasms; State Medicine; Technology; Technology Assessment, Biomedical; Vorinostat
PubMed: 34664200
DOI: 10.1007/s40273-021-01098-3 -
Genes, Chromosomes & Cancer Mar 2003Sézary syndrome (SS) is a rare form of erythrodermic cutaneous T-cell lymphoma with hematological involvement and a poor prognosis. At present little is known about the... (Comparative Study)
Comparative Study Review
Sézary syndrome (SS) is a rare form of erythrodermic cutaneous T-cell lymphoma with hematological involvement and a poor prognosis. At present little is known about the molecular pathogenesis of this malignancy. To address this issue, we analyzed 28 SS cases through the use of molecular cytogenetic techniques. Conventional cytogenetic analysis showed 12 of 28 cases with clonal chromosome abnormalities (43%). Seven cases had aberrations affecting chromosomes 1 and 17; five demonstrated rearrangement of chromosomes 10 and 14; four presented with an abnormality of 6q. Multiplex-fluorescence in situ hybridization (M-FISH) revealed complex karyotypes in 6 of 17 cases (35%), and recurrent der(1)t(1;10)(p2;q2) and der(14)t(14;15)(q;q?) translocations were each identified in two cases, and confirmed by dual-color FISH. There was an overall difference in the incidence of clonal abnormalities detected by G-banded karyotyping and M-FISH. In addition, comparative genomic hybridization studies revealed chromosome imbalances (CIs) in 9 of 20 cases (45%), with a mean DNA copy number change per sample of 1.95 +/- 2.74, and losses (mean: 1.25 +/- 1.77) more frequent than gains (mean: 0.7 +/- 1.26). The most common CIs noted were loss of 1p, followed by losses of 10/10q, 17p, and 19, and gains of 17q and 18. Furthermore, in conjunction with this study a systematic literature review was conducted, which showed a high frequency and consistent pattern of chromosome changes in SS. These findings suggest that chromosomal instability is common in SS, although there are specific chromosomal abnormalities that appear to be characteristic, and the identification of two different recurrent chromosome translocations provides the basis for further studies.
Topics: Chromosome Aberrations; Chromosome Banding; Chromosome Deletion; Chromosome Painting; Cytogenetic Analysis; Female; Gene Amplification; Humans; In Situ Hybridization, Fluorescence; Male; Nucleic Acid Hybridization; Sezary Syndrome; Translocation, Genetic
PubMed: 12557225
DOI: 10.1002/gcc.10152 -
Journal of the European Academy of... Jan 2024Mogamulizumab is a first-in-class IgG1k monoclonal antibody that selectively targets the chemokine receptor type 4. The drug has received Food and Drug administration... (Review)
Review
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.
PubMed: 38279614
DOI: 10.1111/jdv.19801 -
Journal of the American Academy of... Dec 2015Leonine facies (LF) is defined as displaying facial features similar to that of a lion with prominent convexities and furrowed creases. LF develops in a very small... (Review)
Review
BACKGROUND
Leonine facies (LF) is defined as displaying facial features similar to that of a lion with prominent convexities and furrowed creases. LF develops in a very small population of patients with cutaneous T-cell lymphoma.
OBJECTIVE
We aimed to study the clinicopathologic features and overall prognosis associated with LF in patients with mycosis fungoides and Sézary syndrome.
METHODS
We conducted a single-center retrospective study, reviewing 1338 patients with mycosis fungoides seen from 1987 to 2015 at a tertiary referral center for cutaneous T-cell lymphoma, and a systematic review of 14 patients in the literature.
RESULTS
We identified 10 patients with mycosis fungoides who developed LF. Folliculotropism was seen in all patients with LF who had facial biopsy specimens. Radiation was a beneficial therapy. Complete remission was achieved in 1 patient and overall 5-year survival was 26%. Systematic review of 10 additional patients showed that all patients with LF, including ours, had stage-IV disease and some degree of blood involvement, but not all met criteria for Sézary syndrome.
LIMITATIONS
This was a retrospective study with a small sample size.
CONCLUSION
LF is associated with stage-IV cutaneous T-cell lymphoma, is often accompanied by folliculotropism and blood involvement, and can be treated with local electron beam therapy.
Topics: Adult; Aged; Biopsy, Needle; Cancer Care Facilities; Cohort Studies; Combined Modality Therapy; Facies; Female; Follow-Up Studies; Humans; Immunohistochemistry; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Mycosis Fungoides; Neoplasm Invasiveness; Neoplasm Staging; Positron-Emission Tomography; Retrospective Studies; Risk Assessment; Skin Neoplasms; Survival Rate; Tertiary Care Centers; Treatment Outcome
PubMed: 26476898
DOI: 10.1016/j.jaad.2015.09.017 -
European Journal of Dermatology : EJD Dec 2018The efficacy of alemtuzumab for the treatment of refractory Sézary syndrome (SS) versus other third-line agents such as pralatrexate and gemcitabine is poorly... (Comparative Study)
Comparative Study
The efficacy of alemtuzumab for the treatment of refractory Sézary syndrome (SS) versus other third-line agents such as pralatrexate and gemcitabine is poorly characterized. To elucidate the effectiveness of alemtuzumab versus other third-line options for the treatment of refractory SS, we conducted a meta-analysis of existing data. A systematic review was performed in March 2017 based on a search using Ovid-MEDLINE and OVID-EMBASE for articles evaluating single-agent alemtuzumab, gemcitabine, or pralatrexate for the treatment of SS and mycosis fungoides (MF). Twenty-two publications were identified that fulfilled all search criteria (total n = 323 patients), with six publications of lower quality being excluded from our analysis in order to decrease the risk of bias (final: n = 308 patients; 93 with SS and 147 with MF). Across all studies, alemtuzumab was significantly more effective in patients with SS (overall response rate [ORR]: 81%; complete response rate [CRR]: 38%) than patients with MF (ORR: 29%; CRR: 8%). However, gemcitabine was more effective than alemtuzumab or pralatrexate in treating MF. Alemtuzumab-treated patients had more frequent side effects, which were influenced by route of administration and dose. There was a lower incidence of lymphopenia and other serious adverse events in patients treated with subcutaneous (38%) compared to intravenous regimens (68%), and lower-dose (5%) compared to high-dose alemtuzumab regimens (54%). No significant differences were found in the effectiveness of different routes of administration or dosing regimens. Our review supports the use of low-dose subcutaneous alemtuzumab as a third-line treatment for SS.
Topics: Alemtuzumab; Aminopterin; Antimetabolites, Antineoplastic; Antineoplastic Agents, Immunological; Deoxycytidine; Folic Acid Antagonists; Humans; Mycosis Fungoides; Retreatment; Sezary Syndrome; Skin Neoplasms; Gemcitabine
PubMed: 30591425
DOI: 10.1684/ejd.2018.3444 -
American Journal of Clinical Dermatology Mar 2023Cutaneous T-cell lymphoma following biologic therapy is extremely rare.
BACKGROUND
Cutaneous T-cell lymphoma following biologic therapy is extremely rare.
OBJECTIVE
The aim of this systematic review was to investigate the development of cutaneous T-cell lymphoma (CTCL) following treatment with a biologic agent.
METHODS
A systematic literature review was performed for patients who developed CTCL after exposure to biologic therapy. Works were limited to English language and excluded animal studies, guidelines, and protocols. Potentially eligible titles were identified using controlled vocabulary in tandem with key words. The search strategy was peer-reviewed prior to execution.
RESULTS
Twenty-eight total studies revealed sixty-two patients who developed CTCL following exposure to a biologic agent. Of these, 44% were Caucasian, and the median age at diagnosis was 56 years. Seventy-six percent of patients received biologic therapy for a primary inflammatory skin condition. Dupilumab was the most reported (42%) agent amongst the cohort. The median time from initiation of the biologic agent to diagnosis of CTCL in these cases was 4 months (range: 0-84). Mycosis fungoides (65%) and Sézary syndrome (10%) were the most common subtypes of CTCL diagnosed. Twenty-one (34%) patients were reported to be alive with disease, outcome was not reported in 21 patients (34%), ten patients (16%) were alive and in complete remission, eight patients (13%) died of disease and two patients (3%) died due to other causes.
CONCLUSION
While biologic agents may have a role in the development of CTCL, in order to definitively elucidate their role, more methodologically robust studies (such as those that utilize population databases) would need to occur.
Topics: Humans; Middle Aged; Skin Neoplasms; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Biological Factors; Biological Products
PubMed: 36627479
DOI: 10.1007/s40257-022-00749-1