TY - JOUR
T1 - Immune-related adverse events of dendritic cell vaccination correlate with immunologic and clinical outcome in stage III and IV melanoma patients
AU - Boudewijns, Steve
AU - Westdorp, Harm
AU - Koornstra, Rutger H.T.
AU - Aarntzen, Erik H.J.G.
AU - Schreibelt, Gerty
AU - Creemers, Jeroen H.A.
AU - Punt, Cornelis J.A.
AU - Figdor, Carl G.
AU - De Vries, I. Jolanda M.
AU - Gerritsen, Winald R.
AU - Bol, Kalijn F.
N1 - Publisher Copyright:
© Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016
Y1 - 2016
N2 - The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flulike symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8+ T cells (both P<0.001). In stage III melanoma patients experiencing flulike symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome.
AB - The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flulike symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8+ T cells (both P<0.001). In stage III melanoma patients experiencing flulike symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome.
KW - Dendritic cell vaccination
KW - Immune response
KW - Immune-related adverse events
KW - Melanoma
UR - http://www.scopus.com/inward/record.url?scp=84969922441&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84969922441&partnerID=8YFLogxK
U2 - 10.1097/CJI.0000000000000127
DO - 10.1097/CJI.0000000000000127
M3 - Article
C2 - 27227325
AN - SCOPUS:84969922441
SN - 1524-9557
VL - 39
SP - 241
EP - 248
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
IS - 6
ER -