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Actas Dermo-sifiliograficas Feb 2024The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture...
BACKGROUND AND OBJECTIVE
The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis.
METHODS
We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS).
RESULTS
A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each.
CONCLUSIONS
The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.
Topics: Adult; Humans; Male; Middle Aged; Female; Quality of Life; Spain; Skin Neoplasms; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome
PubMed: 37689349
DOI: 10.1016/j.ad.2023.08.007 -
Cancers Sep 2023(MF) and (SS) are the most common types of primary cutaneous T-cell lymphoma (CTCL). Proliferating cell nuclear antigen (PCNA) is expressed on the cell surface of...
(MF) and (SS) are the most common types of primary cutaneous T-cell lymphoma (CTCL). Proliferating cell nuclear antigen (PCNA) is expressed on the cell surface of cancer cells (csPCNA), but not on normal cells. It functions as an immune checkpoint ligand by interacting with natural killer (NK) cells through the NK inhibitory receptor NKp44, leading to the inhibition of NK cytotoxicity. A monoclonal antibody (mAb14) was established to detect csPCNA on cancer cells and block their interaction with NKp44. In this study, three CTCL cell lines and peripheral blood mononuclear cells (PBMCs) from patients with SS and healthy donors were analyzed for csPCNA using mAb14, compared to monoclonal antibody PC10, against nuclear PCNA (nPCNA). The following assays were used: immunostaining, imaging flow cytometry, flow cytometry, cell sorting, cell cycle analysis, ELISA, and the NK-cell cytotoxic assay. mAb14 successfully detected PCNA on the membrane and in the cytoplasm of viable CTCL cell lines associated with the G2/M phase. In the Sézary PBMCs, csPCNA was expressed on lymphoma cells that had an atypical morphology and not on normal cells. Furthermore, it was not expressed on PBMCs from healthy donors. In the co-culture of peripheral blood NK (pNK) cells with CTCL lines, mAb14 increased the secretion of IFN-γ, indicating the reactivation of pNK activity. However, mAb14 did not enhance the cytotoxic activity of pNK cells against CTCL cell lines. The unique expression of csPCNA detected by mAb14 suggests that csPCNA and mAb14 may serve as a potential biomarker and tool, respectively, for detecting malignant cells in SS and possibly other CTCL variants.
PubMed: 37686697
DOI: 10.3390/cancers15174421 -
JID Innovations : Skin Science From... Sep 2023The genomic basis of cutaneous T-cell lymphoma has been characterized by gene copy number alterations and genomic sequencing, but there are few clinical tests that are...
The genomic basis of cutaneous T-cell lymphoma has been characterized by gene copy number alterations and genomic sequencing, but there are few clinical tests that are being widely used to inform the diagnosis and prognosis of leukemic cutaneous T-cell lymphoma that may arise as a progression from mycosis fungoides or de novo as Sézary syndrome. An 11-gene FISH panel of , , , , , , , and deletions and , (), and amplifications was previously found to encapsulate >95% of gene copy number variations in leukemic cutaneous T-cell lymphoma. Through a retrospective analysis of patients with leukemic cutaneous T-cell lymphoma seen at the Yale Cancer Center from 2014 to 2020, we gathered the relevant genes as they became available and correlated them to factors with prognostic relevance as a proof of concept to show the potential utility in further developing a limited gene panel for prognosis. In this study, we show that the abnormal FISH results show an association with clinically relevant factors (blood stage, CD4:8 ratio, and percentage blood involvement) and have a nonsignificant statistical trend (>90%) toward correlation with overall survival. In addition, the previous cost-effective panels were (), , , and . We now suggest adding and on the basis of our findings.
PubMed: 37674691
DOI: 10.1016/j.xjidi.2023.100212 -
Blood Advances Nov 2023Despite increasing availability of therapies, patients with Sezary syndrome (SS) commonly endure multi-line treatment journeys, mostly with partial responses of short... (Observational Study)
Observational Study
Despite increasing availability of therapies, patients with Sezary syndrome (SS) commonly endure multi-line treatment journeys, mostly with partial responses of short duration. Measuring clinical benefit is challenging; time-to-next-treatment (TTNT) provides a robust, objective measurement of efficacy. This international observational study examines patterns of clinical care and therapeutic benefit as measured by TTNT. TTNT was calculated for monotherapies and combination therapies, with consideration to treatment line. 178 patients with SS (73% de novo, 27% secondary) were included, receiving 721 lines of systemic therapy, with median follow-up of 56.9 months. Across all lines, 58 different therapeutic regimens were prescribed (54 were systemic therapies) and classified into 17 treatment groups. The most common first-line treatments were extracorporeal photopheresis (ECP)-containing combination therapy (20%) and retinoid monotherapy (19%). Median TTNT for all first-line therapies was short (5.4 months). First-line, combination therapies had longer median TTNT than monotherapies, 10.0 vs 5.0 months (P = .004), respectively. Later delivery of combination therapies was associated with shorter clinical benefit, with median TTNT reduced to 6.2 and 2.2 months for mid-line (2nd-4th line) and late-line (≥5th line), respectively (P < .001). First-line ECP-containing treatments were associated with longer median TTNT than non-ECP-containing treatments, 9.0 vs 4.9 months (P = .007). For both ECP-monotherapy and ECP-containing combination therapy, significant reductions in TTNT were seen in later lines. These data suggest therapeutic benefit from first-line delivery of combination therapy for SS and favor early inclusion of ECP in the treatment algorithm for those who can access it.
Topics: Humans; Sezary Syndrome; Skin Neoplasms; Treatment Outcome; Combined Modality Therapy; Photopheresis
PubMed: 37648672
DOI: 10.1182/bloodadvances.2023011041 -
Journal of Comparative Effectiveness... Oct 2023Due to extensive treatment switching in the MAVORIC trial, lack of UK regulatory licence for the comparator, overall survival (OS) with mogamulizumab was compared with...
Due to extensive treatment switching in the MAVORIC trial, lack of UK regulatory licence for the comparator, overall survival (OS) with mogamulizumab was compared with patients with previously treated advanced mycosis fungoides/Sézary syndrome (MF/SS) in real-world setting. Data were from the Hospital Episode Statistics database (all patients in NHS secondary care system in 2009-2019). Patients were selected according to trial inclusion criteria, then trial and HES samples were matched on selected variables with significant imbalance. The analysis indicated significant improvement in OS for mogamulizumab treatment compared with UK clinical practice (hazard ratio: 0.36, 95% CI: 0.24, 0.53). Results suggest an OS advantage for patients with advanced MF/SS treated with mogamulizumab in MAVORIC trial compared with UK clinical practice.
Topics: Humans; Sezary Syndrome; Standard of Care; Skin Neoplasms; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; United Kingdom
PubMed: 37642410
DOI: 10.57264/cer-2023-0017 -
Pharmaceutics Aug 2023The present study describes the development of novel block copolymer nanocarriers of the phytocannabinoid cannabidiol (CBD), designed to enhance the solubility of the...
The present study describes the development of novel block copolymer nanocarriers of the phytocannabinoid cannabidiol (CBD), designed to enhance the solubility of the drug in water while achieving high encapsulation efficiency and prolonged drug release. Firstly, a well-defined amphiphilic block copolymer consisting of two outer hydrophilic polyglycidol (PG) blocks and a middle hydrophobic block of poly(ε-caprolactone) bearing pendant cinnamyl moieties (P(CyCL--CL)) were synthesized by the click coupling reaction of PG-monoalkyne and P(CyCL--CL)-diazide functional macroreagents. A non-modified polyglycidol/poly(ε-caprolactone) amphiphilic block copolymer was obtained as a referent system. Micellar carriers based on the two block copolymers were formed via the solvent evaporation method and loaded with CBD following two different protocols-loading during micelle formation and loading into preformed micelles. The key parameters/characteristics of blank and CBD-loaded micelles such as size, size distribution, zeta potential, molar mass, critical micelle concentration, morphology, and encapsulation efficiency were determined by using dynamic and static multiangle and electrophoretic light scattering, transmission electron microscopy, and atomic force microscopy. Embedding CBD into the micellar carriers affected their hydrodynamic radii to some extent, while the spherical morphology of particles was not changed. The nanoformulation based on the copolymer bearing cinnamyl moieties possessed significantly higher encapsulation efficiency and a slower rate of drug release than the non-modified copolymer. The comparative assessment of the antiproliferative effect of micellar CBD vs. the free drug against the acute myeloid leukemia-derived HL-60 cell line and Sezary Syndrome HUT-78 demonstrated that the newly developed systems have pronounced antitumor activity.
PubMed: 37631342
DOI: 10.3390/pharmaceutics15082128 -
JAAD Case Reports Aug 2023
PubMed: 37600742
DOI: 10.1016/j.jdcr.2023.06.009 -
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