Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Ref Type Journal Article
PMID (29320474)
Authors Eroglu Z, Zaretsky JM, Hu-Lieskovan S, Kim DW, Algazi A, Johnson DB, Liniker E, Ben Kong null, Munhoz R, Rapisuwon S, Gherardini PF, Chmielowski B, Wang X, Shintaku IP, Wei C, Sosman JA, Joseph RW, Postow MA, Carlino MS, Hwu WJ, Scolyer RA, Messina J, Cochran AJ, Long GV, Ribas A
Title High response rate to PD-1 blockade in desmoplastic melanomas.
Journal Vol Issue Date Pages Journal Short Title
Nature 553 7688 2018 Jan 18 347-350 Nature
URL
Abstract Text Desmoplastic melanoma is a rare subtype of melanoma characterized by dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations, and is highly associated with ultraviolet light-induced DNA damage. We analysed sixty patients with advanced desmoplastic melanoma who had been treated with antibodies to block programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1). Objective tumour responses were observed in forty-two of the sixty patients (70%; 95% confidence interval 57-81%), including nineteen patients (32%) with a complete response. Whole-exome sequencing revealed a high mutational load and frequent NF1 mutations (fourteen out of seventeen cases) in these tumours. Immunohistochemistry analysis from nineteen desmoplastic melanomas and thirteen non-desmoplastic melanomas revealed a higher percentage of PD-L1-positive cells in the tumour parenchyma in desmoplastic melanomas (P = 0.04); these cells were highly associated with increased CD8 density and PD-L1 expression in the tumour invasive margin. Therefore, patients with advanced desmoplastic melanoma derive substantial clinical benefit from PD-1 or PD-L1 immune checkpoint blockade therapy, even though desmoplastic melanoma is defined by its dense desmoplastic fibrous stroma. The benefit is likely to result from the high mutational burden and a frequent pre-existing adaptive immune response limited by PD-L1 expression.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CD274 positive malignant spindle cell melanoma predicted - sensitive Pembrolizumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1 blockade therapies including Keytruda (pembrolizumab), Opdivo (nivolumab), and BMS-936559 (alone or in combination) resulted in complete response in 32% (19/60), and partial response in 38% (23/60) of malignant spindle cell melanoma patients, whose tumors contained a high percentage of CD274-positive cells (PMID: 29320474). 29320474
CD274 positive malignant spindle cell melanoma predicted - sensitive Nivolumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1 blockade therapies including Keytruda (pembrolizumab), Opdivo (nivolumab), and BMS-936559 (alone or in combination) resulted in complete response in 32% (19/60), and partial response in 38% (23/60) of malignant spindle cell melanoma patients, whose tumors contained a high percentage of CD274-positive cells (PMID: 29320474). 29320474
CD274 positive malignant spindle cell melanoma predicted - sensitive BMS-936559 Clinical Study - Cohort Actionable In a retrospective analysis, PD-1 blockade therapies including Keytruda (pembrolizumab), Opdivo (nivolumab), and BMS-936559 (alone or in combination) resulted in complete response in 32% (19/60), and partial response in 38% (23/60) of malignant spindle cell melanoma patients, whose tumors contained a high percentage of CD274-positive cells (PMID: 29320474). 29320474