Combining chemotherapy and autologous peptide-pulsed dendritic cells provides survival benefit in stage IV melanoma patients.
Journal
Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG
ISSN: 1610-0387
Titre abrégé: J Dtsch Dermatol Ges
Pays: Germany
ID NLM: 101164708
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
13
03
2020
accepted:
25
08
2020
pubmed:
17
11
2020
medline:
10
8
2021
entrez:
16
11
2020
Statut:
ppublish
Résumé
We examined retrospectively whether the combination of standard dacarbazine (DTIC) and/or fotemustine chemotherapy and autologous peptide-loaded dendritic cell (DC) vaccination may improve survival of stage IV melanoma patients. Furthermore, a small cohort of long-term survivors was studied in more detail. Between 1998 and 2008, 41 patients were vaccinated at least three times with DCs while receiving chemotherapy and compared to all other 168 patients in our database who only received chemotherapy (1993-2008). Median life expectancy of patients receiving additional DC-vaccination was 18 months, compared to eleven months for patients under standard chemotherapy alone. In contrast to patients with other haplotypes, the HLA-A1/A1 subset of DC-treated patients showed significantly lower median survival (12 vs. 25 months). Autoantibodies were frequently detected in serum of both vaccinated and non-vaccinated patients, and there was no correlation between titers, loss or appearance of autoantibodies and survival. Additionally, phenotyping of DCs and PBMCs also did not reveal any conspicuous correlation with survival. Combining standard chemotherapy and DC vaccination appears superior to chemotherapy alone. The impact of HLA haplotypes on survival emphasizes the importance of a careful selection of patients with specific, well-defined HLA haplotypes for future vaccination trials using peptide-pulsed DCs, possibly combined with checkpoint inhibitors.
Sections du résumé
BACKGROUND AND OBJECTIVES
We examined retrospectively whether the combination of standard dacarbazine (DTIC) and/or fotemustine chemotherapy and autologous peptide-loaded dendritic cell (DC) vaccination may improve survival of stage IV melanoma patients. Furthermore, a small cohort of long-term survivors was studied in more detail.
PATIENTS AND METHODS
Between 1998 and 2008, 41 patients were vaccinated at least three times with DCs while receiving chemotherapy and compared to all other 168 patients in our database who only received chemotherapy (1993-2008).
RESULTS
Median life expectancy of patients receiving additional DC-vaccination was 18 months, compared to eleven months for patients under standard chemotherapy alone. In contrast to patients with other haplotypes, the HLA-A1/A1 subset of DC-treated patients showed significantly lower median survival (12 vs. 25 months). Autoantibodies were frequently detected in serum of both vaccinated and non-vaccinated patients, and there was no correlation between titers, loss or appearance of autoantibodies and survival. Additionally, phenotyping of DCs and PBMCs also did not reveal any conspicuous correlation with survival.
CONCLUSIONS
Combining standard chemotherapy and DC vaccination appears superior to chemotherapy alone. The impact of HLA haplotypes on survival emphasizes the importance of a careful selection of patients with specific, well-defined HLA haplotypes for future vaccination trials using peptide-pulsed DCs, possibly combined with checkpoint inhibitors.
Identifiants
pubmed: 33197129
doi: 10.1111/ddg.14334
pmc: PMC7756560
doi:
Substances chimiques
Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1270-1277Subventions
Organisme : Austrian Science Fund FWF
ID : P 29919
Pays : Austria
Informations de copyright
© 2020 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.
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