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Actas Dermo-sifiliograficas Jun 2024Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and...
BACKGROUND AND OBJECTIVES
Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL.
MATERIAL AND METHOD
This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals.
RESULTS
A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported.
CONCLUSIONS
Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.
Topics: Humans; Bexarotene; Male; Female; Aged; Retrospective Studies; Middle Aged; Aged, 80 and over; Skin Neoplasms; Adult; Tetrahydronaphthalenes; Mycosis Fungoides; Sezary Syndrome; Spain; Lymphoma, T-Cell, Cutaneous; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38395224
DOI: 10.1016/j.ad.2023.12.007 -
JAAD Case Reports Feb 2024
PubMed: 38357556
DOI: 10.1016/j.jdcr.2023.12.003 -
The British Journal of Dermatology May 2024The prognosis for Black patients with classical cutaneous T-cell lymphoma (CTCL) [mycosis fungoides (MF) and Sézary syndrome (SS)] is known to be worse than that of...
The prognosis for Black patients with classical cutaneous T-cell lymphoma (CTCL) [mycosis fungoides (MF) and Sézary syndrome (SS)] is known to be worse than that of other ethnicities, but there is a paucity of data on which demographic factors or disease characteristics may contribute to this disparity. In our retrospective cohort study of 229 patients, Black patients experienced poorer overall survival adjusted for confounding variables including demographics and key disease characteristics ( = 0.01), and suffered a significantly higher rate of large-cell transformation when compared with White patients ( = 0.012). Our study suggests that Black patients with MF/SS experience poorer overall survival that cannot be explained by sex, age or CTCL disease characteristics.
Topics: Humans; Skin Neoplasms; Retrospective Studies; Male; Female; Middle Aged; Aged; Black People; Adult; Aged, 80 and over
PubMed: 38282350
DOI: 10.1093/bjd/ljae039 -
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 -
Clinical Lymphoma, Myeloma & Leukemia Apr 2024Clinical presentation of Mycosis fungoides/Sézary syndrome (MF/SS) in Black and African American (AA) patients can be heterogeneous with poor survival reported in... (Observational Study)
Observational Study
BACKGROUND
Clinical presentation of Mycosis fungoides/Sézary syndrome (MF/SS) in Black and African American (AA) patients can be heterogeneous with poor survival reported in AA/black patients. In this study, we aim to characterize differences between AA/black and white patients with MF/SS.
PATIENTS AND METHODS
A retrospective single-center hospital-based case-control study including 292 MF/SS patients (146 AA/black matched with 146 white patients). We analyzed demographic, clinical and survival differences.
RESULTS
AA/black patients were diagnosed at an earlier age (9 years younger), were predominantly females, had higher rates of Medicaid/Medicare insurance and lower income compared to matched white patients (P <.001). Adjusting for age, sex, insurance type, and income bracket, AA/black patients had significantly worse overall survival (hazard ratio [HR] 2.88, 95%CI 1.21-6.85, P = .017). Association of clinical MF phenotype with survival showed that hypopigmentation was associated with survival in AA/black patients but not in white patients. Erythroderma and ulceration were associated with worse survival risk in AA/black patients.
CONCLUSIONS
AA/black patients with MF/SS have a significant worse survival outcome compared to white patients. The association between clinical phenotypes and survival differed between these groups. Further studies are required to investigate whether race-specific pathogenesis or genetic factors may explain these differences.
Topics: Aged; Female; Humans; Male; Case-Control Studies; Lymphoma, T-Cell, Cutaneous; Medicare; Mycosis Fungoides; Retrospective Studies; Sezary Syndrome; Skin Neoplasms; United States
PubMed: 38245472
DOI: 10.1016/j.clml.2023.12.017 -
The Journal of Investigative Dermatology Jul 2024Flow cytometric identification of circulating neoplastic cells (Sezary cells) in patients with mycosis fungoides and Sezary syndrome is essential for diagnosis, staging,...
Flow cytometric identification of circulating neoplastic cells (Sezary cells) in patients with mycosis fungoides and Sezary syndrome is essential for diagnosis, staging, and prognosis. Although recent advances have improved the performance of this laboratory assay, the complex immunophenotype of Sezary cells and overlap with reactive T cells demand a high level of analytic expertise. We utilized machine learning to simplify this analysis using only 2 predefined Sezary cell-gating plots. We studied 114 samples from 59 patients with Sezary syndrome/mycosis fungoides and 66 samples from unique patients with inflammatory dermatoses. A single dimensionality reduction plot highlighted all TCR constant β chain-restricted (clonal) CD3/CD4 T cells detected by expert analysis. On receiver operator curve analysis, an aberrancy scale feature computed by comparison with controls (area under the curve = 0.98) outperformed loss of CD2 (0.76), CD3 (0.83), CD7 (0.77), and CD26 (0.82) in discriminating Sezary cells from reactive CD4 T cells. Our results closely mirrored those obtained by exhaustive expert analysis for event classification (positive percentage agreement = 100%, negative percentage agreement = 99%) and Sezary cell quantitation (regression slope = 1.003, R squared = 0.9996). We demonstrate the potential of machine learning to simplify the accurate identification of Sezary cells.
Topics: Humans; Sezary Syndrome; Flow Cytometry; Skin Neoplasms; Male; Mycosis Fungoides; Female; Middle Aged; Immunophenotyping; Aged; CD4-Positive T-Lymphocytes; Machine Learning; Adult
PubMed: 38237727
DOI: 10.1016/j.jid.2023.12.020 -
Archives of Dermatological Research Jan 2024Cutaneous T-cell lymphomas (CTCL) are a rare group of T-cell neoplasms which infiltrate the skin and can result in substantial morbidity and mortality. Risk factors for...
Cutaneous T-cell lymphomas (CTCL) are a rare group of T-cell neoplasms which infiltrate the skin and can result in substantial morbidity and mortality. Risk factors for CTCL are still poorly understood though recent studies suggest chemical exposures may play a role in its development. To further characterize patient-centered risk factors for CTCL, especially compared with matched controls, we performed one of the largest prospective cohort survey studies to date to examine patient-reported exposures and health-related quality of life (HRQoL) in association with concurrent clinical disease characteristics. Patient demographics, lifestyle factors, and chemical exposures were collected via clinical data and surveys. Descriptive statistics, ANOVA, Chi-square tests and t tests were utilized to compare patient-reported exposures and HRQoL in patients with CTCL versus matched healthy controls (HC). Statistically significant differences were identified between patients and HC in terms of race (non-white race 22.4% in CTCL patients vs. 18.8% in HC, P = 0.01), and education level (high school or less 41.6% in CTCL patients vs. 14.3% in HC, P = 0.001), but not with Fitzpatrick skin type (P = 0.11) or smoking status (P = 0.28). Notably, 36.0% of the CTCL patients reported exposures to chemicals, a near threefold increased percentage when compared to HC (12.9%). Among various chemical exposures, 27.0% of the CTCL patients specifically reported industrial chemical exposure, a more than two-fold increased percentage when compared to HC (12.9%). Itch and pain were significantly associated with skin disease severity (as evaluated by CTCL-specific mSWAT score) in advanced stage disease (stages IIB-IVB) (r = 0.48 and 0.57, P < 0.05). Itch and body mass index (BMI) were weakly associated with skin disease severity in early-stage disease (stages IA-IIA) (r = 0.27 and 0.20, P < 0.05).
Topics: Humans; Cohort Studies; Prospective Studies; Quality of Life; Lymphoma, T-Cell, Cutaneous; Pruritus; Physicians; Skin Neoplasms
PubMed: 38236413
DOI: 10.1007/s00403-023-02799-9 -
American Journal of Ophthalmology Case... Mar 2024To report a case of bilateral peripheral ulcerative keratitis (PUK) in a patient with underlying Sézary syndrome.
PURPOSE
To report a case of bilateral peripheral ulcerative keratitis (PUK) in a patient with underlying Sézary syndrome.
OBSERVATIONS
A 58-year-old male presented with bilateral corneal ulceration with stromal thinning and was diagnosed with PUK. He was actively being treated for Sézary syndrome, a cutaneous T-cell lymphoma. He had no lagophthalmos or other adnexal abnormalities that would lead to ocular surface breakdown. A systemic autoimmune and infectious workup for PUK was unremarkable. His keratitis resolved after treatment with oral prednisone.
CONCLUSIONS AND IMPORTANCE
We describe a previously undocumented association of PUK with Sézary syndrome in a patient without adnexal disease.
PubMed: 38235438
DOI: 10.1016/j.ajoc.2023.101990 -
Expert Review of Anticancer Therapy 2024Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common types of cutaneous T-cell lymphoma. Although many available treatments offer temporary disease... (Review)
Review
INTRODUCTION
Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common types of cutaneous T-cell lymphoma. Although many available treatments offer temporary disease control, allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only curative treatment option for advanced stage MF and SS. CAR T-cell therapy is a promising new avenue for treatment.
AREAS COVERED
In this review, we discuss the evidence supporting the use of allo-HSCT for the treatment of MF/SS, including disease status at the time of transplant, conditioning regimen, total body irradiation (TBI), and donor lymphocyte infusion (DLI). We also address the potential role for CAR T-cell therapy in CTCL.
EXPERT OPINION
Allo-HSCT is an effective treatment for patients with advanced MF and SS. However, significant research is required to determine optimal treatment protocols. Data support the use of reduced-intensity conditioning regimens and suggests that the use of TBI for debulking of skin disease may result in more durable remissions. Donor lymphocyte infusions (DLI) appear to be particularly effective in inducing complete remission in MF/SS patients with relapsed or residual disease. Challenges with CAR-T therapies in T-cell lymphoma include T-cell fratricide due to shared antigens on malignant and nonmalignant T-cells, penetrance into the skin compartment, and CAR-T cell persistence.
Topics: Humans; Skin Neoplasms; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Transplantation, Homologous; Hematopoietic Stem Cell Transplantation
PubMed: 38224371
DOI: 10.1080/14737140.2024.2305356 -
Cancers Dec 2023Primary cutaneous T-cell lymphomas (CTCLs) are rare lymphoproliferative malignancies characterized by significant morbidity and mortality in advanced disease stages. As...
BACKGROUND
Primary cutaneous T-cell lymphomas (CTCLs) are rare lymphoproliferative malignancies characterized by significant morbidity and mortality in advanced disease stages. As curative approaches apart from allogeneic stem cell transplantation are lacking, establishing new treatment options, especially combination therapies, is crucial.
METHODS
This retrospective study included 11 patients with SS or MF receiving therapy with mogamulizumab in combination with ECP from four European expert centers. The response rates in the skin and blood as well as treatment use and adverse events (AE) were described.
RESULTS
8/11 patients (73%) showed an overall response (OR) in the skin. The mean mSWAT decreased from 98.2 ± 40.8 to 34.6 ± 23.8. The overall response rate (ORR) in the blood was 64% with two complete responses. During combination therapy, the mean number of Sézary cells decreased from 3365.3 × 10/L before treatment to 1268.6 × 10/L. The mean minimum known period without progress was 7.2 months in the skin and 7.6 months in the blood. The most common AEs were mogamulizumab-associated rash (MAR) (45.5%), anemia (27.3%), lymphocytopenia (27.8%), and infusion related reaction (16.7%). No AE led to treatment discontinuation.
CONCLUSIONS
Our study presents the combination of mogamulizumab and ECP as an effective therapy in the blood and skin in CTCL with good tolerability, similar to mogamulizumab monotherapy.
PubMed: 38201568
DOI: 10.3390/cancers16010141