-
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 -
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 -
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 -
Critical Reviews in Oncology/hematology Jan 2017Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease... (Review)
Review
BACKGROUND
Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL.
OBJECTIVE
Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30 malignancies in humans.
DATA SOURCES
We searched various databases including PubMed (1946-2015), EMBASE (1947-2015), and Cochrane Central Register of Controlled Trials (1898-2015).
ELIGIBILITY CRITERIA
Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered.
INCLUDED STUDIES
A total of 28 articles met these criteria and are summarized in this manuscript.
CONCLUSION
Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30 malignancies.
Topics: Antineoplastic Agents; Brentuximab Vedotin; Clinical Trials, Phase II as Topic; Humans; Immunoconjugates; Lymphoma, Non-Hodgkin; Neoplasm Recurrence, Local; Prospective Studies
PubMed: 28010897
DOI: 10.1016/j.critrevonc.2016.11.009 -
Dermatologic Therapy Nov 2021Since the emergence of the new coronavirus disease 19 (COVID-19) pandemic, there has been a concern for the patients with chronic autoimmune diseases including...
Since the emergence of the new coronavirus disease 19 (COVID-19) pandemic, there has been a concern for the patients with chronic autoimmune diseases including dermatological conditions over the potential exacerbation of these underlying conditions after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV2). We performed a systematic review to evaluate presentations, postinfection change in the manifestation, diagnosis, and management of flare-ups of underlying dermatologic disease in patients with COVID-19. A total of 17 articles were recovered reporting on flare-ups of dermatological disease including pemphigus vulgaris, psoriasis, subacute cutaneous lupus erythematosus, acrodermatitis continua of Hallopeau, systemic sclerosis sine scleroderma, and Sézary syndrome (SS). Out of these, psoriasis and alopecia areata were the most common conditions. However, most cases of psoriasis could have been attributed to either antimalarial agents that were initially used for the treatment of COVID-19 or discontinuation of treatment following SARS-CoV2 infection.
Topics: COVID-19; Humans; Pandemics; Psoriasis; RNA, Viral; SARS-CoV-2
PubMed: 34453380
DOI: 10.1111/dth.15113 -
Cancers Oct 2020Cutaneous T-cell lymphomas (CTCL) are a heterogenous group of rare diseases. Many studies have reported on local epidemiology or geographic clustering, however we lack...
Cutaneous T-cell lymphomas (CTCL) are a heterogenous group of rare diseases. Many studies have reported on local epidemiology or geographic clustering, however we lack information from a global perspective. A systematic review and meta-analysis was conducted in Medline and the Cochrane Library based on a previously registered protocol and according to the preferred reporting of items for systematic reviews and meta-analyses (PRISMA). We selected publications that enrolled at least 100 patients with primary cutaneous lymphomas according to the current classifications. The relative frequencies (proportions) of subtypes were compared between studies and geographic regions in a meta-analysis. In total, 26 studies met our inclusion criteria, reporting on altogether 16,953 patients. Within primary cutaneous lymphomas, CTCL appeared to be 15% more frequent in Asian populations. Mycosis fungoides (MF) accounted for 62% of CTCL, with an important heterogeneity in frequencies between studies and continents. The proportion of Sézary syndrome (SS) was 3%, stable worldwide. Rare CTCL, such as NK/T-cell lymphoma or subcutaneous panniculitis-like lymphoma, were more frequent in Asian studies. This global meta-analysis of CTCL confirmed the predominance of CTCL among primary cutaneous lymphomas (83% on average) in the three analyzed continents, most of which were MF cases. It revealed the same proportions of SS across continents, and the heterogeneity of MF frequencies, suggesting the possible role of environmental factors in the pathophysiology of the latter. Registration number: CRD42020148295 (PROSPERO).
PubMed: 33050643
DOI: 10.3390/cancers12102921 -
Biology of Blood and Marrow... Jan 2020Mycosis fungoides and Sézary syndrome are the most common types of primary cutaneous T cell lymphomas. The clinical presentation of mycosis fungoides is generally... (Meta-Analysis)
Meta-Analysis
Mycosis fungoides and Sézary syndrome are the most common types of primary cutaneous T cell lymphomas. The clinical presentation of mycosis fungoides is generally indolent, whereas Sézary syndrome represents a more aggressive disease variant. Stage at diagnosis is the most important determinant of long-term survival outcome. Although most patients present with early-stage disease, those who develop progressive disease or have an advanced stage represent a therapeutic challenge because of a lack of effective therapies. Allogeneic hematopoietic cell transplantation (allo-HCT) has been used as a potentially curative treatment modality with encouraging long-term outcomes. However, a lack of randomized controlled data remains, and the published literature is limited to mostly retrospective studies. We performed a comprehensive search of the medical literature using PubMed/Medline, EMBASE, and Cochrane reviews on September 13, 2018. We extracted data on clinical outcomes related to benefits (overall [OS] and progression-free [PFS] survival) and harms (relapse and nonrelapse mortality [NRM]) independently by 2 authors. Our search strategy identified 289 references. Five studies (266 patients) were included in this systematic review and meta-analysis. Reduced-intensity and nonmyeloablative regimens were more commonly prescribed (76%). Mobilized peripheral blood stem cells were the preferred graft source (78%). The pooled OS and PFS rates were 59% (95% confidence interval [CI], 50% to 69%) and 36% (95% CI, 27% to 45%), respectively. Pooled relapse rate was 47% (95% CI, 41% to 53%) and pooled NRM rate 19% (95% CI, 13% to 27%). Results of this systematic review and meta-analysis show that allo-HCT yields encouraging OS and PFS rates; however; relapse remains a significant cause of allo-HCT failure. Novel strategies to further improve outcomes should focus on offering allo-HCT before the development of resistant disease and reducing relapse by incorporating post-transplant maintenance therapies.
Topics: Allografts; Disease-Free Survival; Humans; Maintenance Chemotherapy; Mycosis Fungoides; Peripheral Blood Stem Cell Transplantation; Recurrence; Sezary Syndrome; Survival Rate
PubMed: 31494227
DOI: 10.1016/j.bbmt.2019.08.019 -
JAMA Dermatology Mar 2019Phototherapy is one of the mainstays of treatment for early mycosis fungoides (MF). The most common modalities are psoralen-UV-A (PUVA) and narrowband UV-B (NBUVB). (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Phototherapy is one of the mainstays of treatment for early mycosis fungoides (MF). The most common modalities are psoralen-UV-A (PUVA) and narrowband UV-B (NBUVB).
OBJECTIVE
To compare the efficacy and adverse effects of PUVA vs NBUVB in early-stage MF.
DATA SOURCES
A systematic review was performed by searching Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Ovid Medline, PubMed, Cochrane Library, American College of Physicians ACP Journal Club, and Database of Abstracts of Review of Effectiveness from inception to March 30, 2018. UV A, PUVA, mycosis fungoides, Sézary syndrome, cutaneous T-cell lymphoma, UV B, and UVB were used as either key words or MeSH terms.
STUDY SELECTION
Studies of cohorts with histologically confirmed early-stage MF, defined as stages IA, IB, and IIA, that compared PUVA vs NBUVB, had at least 10 patients in each comparator group, and reported outcomes of response to therapy. Exclusion criteria were studies with patients with stage IIB or higher MF, pediatric patients, fewer than 10 in each comparator group, noncomparative studies, case reports, and abstract studies.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were pooled using a random-effects model with odds ratio (OR) as effect size.
MAIN OUTCOMES AND MEASURES
Main outcomes were complete response rate, partial response rate, disease recurrence, and adverse effects, including erythema, nausea, pruritus, phototoxic effects, dyspepsia, and pain.
RESULTS
Seven studies were included with a total of 778 patients (405 of 724 [55.9%] men; mean age, 52 years); 527 were treated with PUVA and 251 with NBUVB. Most of the included studies were of poor to moderate quality. Any response was found in 479 of the 527 (90.9%) patients treated with PUVA vs 220 of 251 (87.6%) treated with NBUVB (OR, 1.40; 95% CI, 0.84-2.34; P = .20). Complete response was found in 389 of 527 (73.8%) patients who received PUVA vs 156 of 251 (62.2%) who received NBUVB, which was statistically significant (OR, 1.68; 95% CI, 1.02-2.76; P = .04). Partial response was similar (90 of 501 [18.0%] vs 64 of 233 [27.5%]; OR, 0.58; 95% CI, 0.33-1.04; P = .07). No significant difference was found between PUVA and NBUVB in terms of adverse effects of erythema (38 of 527 [7.2%] vs 17 of 251 [6.7%]; P = .54), nausea (10 of 527 [1.9%] vs 3 of 251 [1.2%]; P = .72), pruritus (2 of 527 [0.4%] vs 4 of 251 [1.7%]; P = .26), phototoxic effects (7 of 527 [1.4%] vs 2 of 251 [0.9%]; P = .72), dyspepsia (6 of 527 [1.2%] vs 0 of 251 [0%]; P = .59), or pain (0 of 527 [0%] vs 2 of 251 [0.9%]; P = .50).
CONCLUSIONS AND RELEVANCE
The findings suggest that PUVA is a potential alternative to NBUVB in the management of early-stage MF. These findings have implications for clinicians involved in the management of early-stage MF.
Topics: Aged; Female; Ficusin; Humans; Male; Middle Aged; Mycosis Fungoides; PUVA Therapy; Prognosis; Skin Neoplasms; Treatment Outcome; Ultraviolet Therapy
PubMed: 30698622
DOI: 10.1001/jamadermatol.2018.5204