A paradigm shift in understanding vulvovaginal melanoma as a distinct tumor type compared with cutaneous melanoma.

Autor: Wilhite AM; University of South Alabama, Mitchell Cancer Institute, Division of Gynecologic Oncology. Electronic address: Awilhite@health.southalabama.edu., Wu S; Caris Life Sciences., Xiu J; Caris Life Sciences., Gibney GT; Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital., Phung T; University of South Alabama, Mitchell Cancer Institute, Department of Pathology., In GK; University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, Division of Oncology., Herzog TJ; University of Cincinnati, University of Cincinnati Cancer Center, Division of Gynecologic Oncology., Khabele D; Washington University, Division of Gynecologic Oncology., Erickson BK; University of Minnesota, Division of Gynecologic Oncology., Brown J; Atrium Health, Levine Cancer Institute, Division of Gynecologic Oncology., Rocconi RP; University of Mississippi Medical Center, Division of Gynecologic Oncology., Pierce JY; University of South Alabama, Mitchell Cancer Institute, Division of Gynecologic Oncology., Scalici JM; University of South Alabama, Mitchell Cancer Institute, Division of Gynecologic Oncology., Jones NL; University of South Alabama, Mitchell Cancer Institute, Division of Gynecologic Oncology.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2024 Sep; Vol. 188, pp. 13-21. Date of Electronic Publication: 2024 Jun 10.
DOI: 10.1016/j.ygyno.2024.06.002
Abstrakt: Objective: Our goal was to compare molecular and immune profiles of vulvovaginal melanoma (VVM) with cutaneous melanoma (CM) and explore the significance of immune checkpoint inhibitor (ICI) agents on survival.
Methods: Samples from VVM and CM tumors underwent comprehensive molecular and immune profiling. Treatment and survival data were extracted from insurance claims data and OS was calculated from time of ICI treatment to last contact. Statistical significance was determined using chi-square and Wilcoxon rank sum test and adjusted for multiple comparisons.
Results: Molecular analysis was performed on 142 VVM and 3823 CM tumors. VVM demonstrated significantly (q < 0·01) less frequent BRAF and more frequent KIT, ATRX, and SF3B1 mutations. Alterations in pathways involving DNA damage and mRNA splicing were more common in VVM, while alterations in cell cycle and chromatin remodeling were less common. Immunogenicity of VVM was lower than CM, with an absence of high TMB (0% vs 46.9%) and lower PD-L1 positivity (18·0% vs 29·5%). Median immune checkpoint gene expression was lower in VVM, as were cell fractions for type I macrophages and CD8+ T-cells(q < 0·01). Myeloid dendritic cells were increased in VVM(q < 0·01). Median OS was shorter for VVM than for CM patients treated with ICIs (17·6 versus 37·9 months, HR:1·65 (95% CI 1·02-2·67) p = 0·04).
Conclusions: VVM has a distinct molecular and immune profile compared to CM, which may contribute to the worse survival in VVM compared to CM patients treated with ICI therapy. Though ICIs have been a mainstay of treatment in recent years, our findings suggest that new therapeutic strategies are needed.
Competing Interests: Declaration of competing interest SW and JX are employees of Caris Life Sciences. GTG reports grants from Exelixis and Luceno Dynamics; fees for consulting for Bristol Myers Squibb, Merck, Novartis, Regeneron, Immunocore, Iovance, Lyell Immunopharma, Eisai, Incyte, Pfizer, Sapience Therapeutics, Exicure, and Genentech; fees for payment/honoraria from Immunocore; fees for participation on a Data Safety Monitoring Board/Advisory Board for Huyabio. GKI reports fees for consulting for Sanofi and Pfizer; fees for payment/honoraria from Merck, Sanofi, and Regeneron; fees for support for attending meetings from BMS and Sanofi; fees for participation on a Data Safety Monitoring Board/Advisory Board from Replimune, Castle, and Regeneron; institutional research support from BMS, Regeneron, Replimune, Pfizer, InstilBio, Checkmate Pharmaceuticals, and Xencor. TJH reports consulting fees from J & J, Clovis, AstraZeneca, GSK, Roche Genentech, Caris, Genelux, Aravive, Merck, Eisai, and Seagen. BKE reports fees for participation on a Data Safety Monitoring Board/Advisory Board for Merck and GSK. JB reports fees for consulting for Caris, AstraZeneca, Genentech, GSK Tesaro, and Verastem; fees for participation on a Data Safety Monitoring Board/Advisory Board from Caris, AstraZeneca, GSK Tesaro, and Verastem; fees for a leadership/fiduciary role from American Association of Gynecologic Laparoscopy, and Society of Gynecologic Oncology. The remaining authors have nothing to disclose. All of these disclosures mentioned above are unrelated to this study. No author declares a conflict of interest related to the study.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE