Inflammatory adverse events are associated with disease-free survival after vaccine therapy among patients with melanoma.
Ann Surg Oncol
; 21(12): 3978-84, 2014 Nov.
Article
en En
| MEDLINE
| ID: mdl-24841355
ABSTRACT
BACKGROUND:
Multipeptide vaccines for melanoma may cause inflammatory adverse events (IAE). We hypothesize that IAE are associated with a higher rate of immune response (IR) to vaccination and improved clinical outcomes.METHODS:
Adult patients with resected, high-risk (stage IIB to IV) melanoma were vaccinated with a combination of 12 class I major histocompatibility complex (MHC)-restricted melanoma epitopes, and IAE were recorded. A separate category for hypopigmentation (vitiligo) was also assessed. CD8(+) T cell IR was assessed by direct interferon gamma ELISpot analysis. Overall survival and disease-free survival were analyzed by Cox proportional hazard modeling.RESULTS:
Out of 332 patients, 57 developed IAE, the majority of which were dermatologic (minimum Common Terminology Criteria for Adverse Events [CTCAE] grade 3). Most nondermatologic IAE were CTCAE grade 1 and 2. Vitiligo developed in 23 patients (7 %). A total of 174 patients (53 %) developed a CD8(+) response. Presence of IAE was significantly associated with development of IR (70 vs. 49 %, p = 0.005) and with disease-free survival (hazard ratio 0.54, p = 0.043). There were no significant associations relating vitiligo or IR alone with clinical outcomes.CONCLUSIONS:
IAE are associated with a higher rate of CD8(+) T cell response after vaccination therapy for high-risk melanoma. Our findings suggest either that antitumor activity induced by class I MHC-restricted peptide vaccines may depend on immunologic effects beyond simple expansion of CD8(+) T cells or that the intrinsic inflammatory response of patients contributes to clinical outcome in melanoma.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedades de la Piel
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Inmunoterapia Activa
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Inflamación
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Enfermedades Pulmonares
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Melanoma
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Ann Surg Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2014
Tipo del documento:
Article