Inflammatory adverse events are associated with disease-free survival after vaccine therapy among patients with melanoma.

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.

• Authors: Yinin Hu, Mark E Smolkin, Emily J White, Gina R Petroni, Patrice Y Neese, Craig L Slingluff Jr
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 21 Issue 12 Pg. 3978-84 (Nov 2014) ISSN: 1534-4681 [Electronic] United States
• PMID: 24841355 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Histocompatibility Antigens Class I

Topics

• Adult
• Antigens, Neoplasm (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Female
• Follow-Up Studies
• Histocompatibility Antigens Class I (immunology)
• Humans
• Immunotherapy, Active (adverse effects)
• Inflammation (diagnosis, etiology, mortality)
• Lung Diseases (diagnosis, etiology, mortality)
• Male
• Melanoma (complications, immunology, mortality, therapy)
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Neoplasm Staging
• Prognosis
• Skin Diseases (diagnosis, etiology, mortality)
• Survival Rate