Pembrolizumab in mycosis fungoides with PD-L1 structural variants.
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ABSTRACT:
SUBMITTER: Beygi S
PROVIDER: S-EPMC7876893 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC7389258 | biostudies-literature
Project description:PurposeTo assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS).Patients and methodsCITN-10 is a single-arm, multicenter phase II trial of 24 patients with advanced MF or SS. Patients were treated with pembrolizumab 2 mg/kg every 3 weeks for up to 24 months. The primary end point was overall response rate by consensus global response criteria.ResultsPatients had advanced-stage disease (23 of 24 with stage IIB to IV MF/SS) and were heavily pretreated with a median of four prior systemic therapies. The overall response rate was 38% with two complete responses and seven partial responses. Of the nine responding patients, six had 90% or more improvement in skin disease by modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached, with a median response follow-up time of 58 weeks. Immune-related adverse events led to treatment discontinuation in four patients. A transient worsening of erythroderma and pruritus occurred in 53% of patients with SS. This cutaneous flare reaction did not result in treatment discontinuation for any patient. The flare reaction correlated with high PD-1 expression on Sézary cells but did not associate with subsequent clinical responses or lack of response. Treatment responses did not correlate with expression of PD-L1, total mutation burden, or an interferon-? gene expression signature.ConclusionPembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS.
| S-EPMC6943974 | biostudies-literature
Project description:Mycosis fungoides (MF) is the most common and best studied of cutaneous T-cell lymphoma (CTCL). Three clinical cutaneous stages have been described (patch, plaque and tumor) as the disease progress developing also the disease lymph node, peripheral blood or systemic involvement in late stages. Clinical and pathologic diagnosis of early MF stages (patch and plaque) is difficult as its morphologic similarity to inflammatory dermatoses and low proportion of tumoral cells.
2018-06-21 | GSE109421 | GEO
Project description:BackgroundMycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, for which there is no cure. Immune checkpoint inhibitors have been tried in MF but the results have been inconsistent. To gain insight into the immunogenicity of MF we characterized the neoantigen landscape of this lymphoma, focusing on the known predictors of responses to immunotherapy: the quantity, HLA-binding strength and subclonality of neoantigens.MethodsWhole exome and whole transcriptome sequences were obtained from 24 MF samples (16 plaques, 8 tumors) from 13 patients. Bioinformatic pipelines (Mutect2, OptiType, MuPeXi) were used for mutation calling, HLA typing, and neoantigen prediction. PhyloWGS was used to subdivide malignant cells into stem and clades, to which neoantigens were matched to determine their clonality.ResultsMF has a high mutational load (median 3,217 non synonymous mutations), resulting in a significant number of total neoantigens (median 1,309 per sample) and high-affinity neoantigens (median 328). In stage I disease most neoantigens were clonal but with stage progression, 75% of lesions had >50% subclonal antigens and 53% lesions had CSiN scores <1. There was very little overlap in neoantigens across patients or between different lesions on the same patient, indicating a high degree of heterogeneity.ConclusionsThe neoantigen landscape of MF is characterized by high neoantigen load and significant subclonality which could indicate potential challenges for immunotherapy in patients with advanced-stage disease.
| S-EPMC7719792 | biostudies-literature
Project description:Cutaneous T-cell lymphomas are a heterogeneous collection of non-Hodgkin lymphomas that arise from skin-tropic memory T lymphocytes. Among them, mycosis fungoides (MF) and Sézary syndrome (SS) are the most common malignancies. Diagnosis requires the combination of clinical, pathologic, and molecular features. Significant advances have been made in understanding the genetic and epigenetic aberrations in SS and to some extent in MF. Several prognostic factors have been identified. The goal of treatment is to minimize morbidity and limit disease progression. However, hematopoietic stem cell transplantation, considered for patients with advanced stages, is the only therapy with curative intent.
| S-EPMC7147244 | biostudies-literature
Project description:MicroRNAs (miRNAs) are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many malignancies including lymphoma. However, the role of miRNAs in the pathogenesis of T-cell lymphoid malignancies is poorly understood. Previously we examined the miRNA profile of Sézary syndrome (Sz), a leukemia of skin-homing memory T cells. In this study we determined the complete miRNome of mycosis fungoides (MF), the most common type of cutaneous T cell lymphoma. The miRNA profile of skin biopsies from 19 patients with tumor stage MF and 12 patients with benign inflammatory dermatoses (eczema and lichen planus) were compared by microarray analysis. We identified 49 miRNAs that are differentially expressed in tumor stage MF compared to benign inflammatory dermatoses using ANOVA analysis (P < 0.05, Benjamini-Hochberg corrected). The majority of the differentially expressed miRNAs (30/49) were up-regulated in tumor stage MF. The most significant differentially expressed were miR-155 and miR-92a (both up-regulated in tumor stage MF), while miR-93 showed the highest up-regulation in tumor stage MF with a fold difference of 5.8. Differential expression of a selection of these miRNAs was validated by miRNA-Q-PCR on additional test groups (tumors and controls). None of the miRNAs up-regulated in tumor stage MF was previously shown to be up-regulated in Sz, and only 2 of the 19 miRNAs down-regulated in tumor stage MF were also down-regulated in Sz. Taken together this report is the first describing the miRNA signature of tumor stage MF.
| S-EPMC5528293 | biostudies-other
Project description:Differentiating early mycosis fungoides (MF) from inflammatory dermatitis is a challenge. We compare the differential expression profile of early-stage MF samples and benign inflammatory dermatoses using microRNA (miRNA) arrays. 114 miRNAs were found to be dysregulated between these entities. The seven most differentially expressed miRNAs between these two conditions were further analyzed using RT-PCR in two series comprising 38 samples of early MFs and 18 samples of inflammatory dermatitis. A series of 51 paraffin-embedded samples belonging to paired stages of 16 MF patients was also analyzed. MiRNAs 26a, 222, 181a and 146a were differentially expressed between tumoral and inflammatory conditions. Two of these miRNAs (miRNA-181a and miRNA-146a) were significantly deregulated between early and advanced MF stages. Bioinformatic analysis showed FOXP3 expression to be regulated by these miRNAs. Immunohistochemistry revealed the level of FOXP3 expression to be lower in tumoral MFs than in plaque lesions in paraffin-embedded tissue. A functional study confirmed that both miRNAs diminished FOXP3 expression when overexpressed in CTCL cells. The data presented here suggest that the analysis of a restricted number of miRNAs (26a, 222, 181a and 146a) could be sufficient to differentiate tumoral from reactive conditions. Moreover, these miRNAs seem to be involved in MF progression.
| S-EPMC5997347 | biostudies-literature
Project description:Mycosis fungoides is the most common primary cutaneous T-cell lymphoma. The approach to diagnosis and further follow-up is outlined. Evidence for interventions is based classically on a Tumor Node Metastasis Blood TNMB "stage-based" approach. The treatment options in India are limited. The options as per risk stratification and prognostic index are discussed. Early stages and low-risk patients can be managed with expectant policy or skin-directed therapies including topical steroids and phototherapy; intermediate-risk patients can be opted for interferons or retinoids or low dose methotrexate along with radiotherapy including total skin electron beam therapy while high-risk patients are managed most often with single agent or multiagent palliative chemotherapy. Patients who are intermediate- or high-risk need management by a multispecialty team at tertiary care centers.
| S-EPMC5363136 | biostudies-other
Project description:Introduction. Mycosis fungoides (MF) is a form of primary cutaneous T-cell lymphomas, and radiotherapy (RT) has been used to treat localized/limited lesions of MF. In this case report, the results of low-dose RT applied for palliative purpose are shared. Case Report. A 70-year-old male patient was admitted to the outpatient clinic 7 months ago with a generalized itchy rash. The result of the biopsy was reported as mycosis fungoides. Systemic treatment was not performed due to comorbid diseases. The hemibody RT was applied. 2?Gy was given per fraction, with a total dose of 6?Gy. The significant clinical relief was observed with 6?Gy RT. The patient died due to multiorgan failure 2 months later, and no recurrence was observed. Conclusion. The palliation was achieved in the advanced MF patient with fractionated 6?Gy hemibody RT for the remaining 2 months of life.
| S-EPMC7128043 | biostudies-literature