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Inflammatory Adverse Events are Associated with Disease-Free Survival after Vaccine Therapy among Patients with Melanoma

  • Melanomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgment

Funded in part by NIH/NCI grants NIH R01 CA057653 and CA118386, and NIH R21 CA103528 (to CLS), and NIH T32 CA163177 (to YH). Support was also provided by the University of Virginia Cancer Center Support Grant (NIH/NCI P30 CA44579, Clinical Trials Office, Tissue Procurement Facility, and Biomolecular Core Facility); and the UVA General Clinical Research Center (NIH M01 RR00847). Peptides used in the vaccines were prepared with philanthropic support from the Commonwealth Foundation for Cancer Research and Alice and Bill Goodwin. Additional philanthropic support was provided by Frank and Jane Batten, the James and Rebecca Craig Foundation, George S. Suddock, Richard and Sherry Sharp, and the Patients and Friends Research Fund of the University of Virginia Cancer Center.

Disclosure

CLS is an inventor for peptides included in these trials; the patents are held by the University of Virginia Licensing and Ventures Group. The other authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Surgery/Division of Surgical Oncology, University of Virginia Health System, Charlottesville, VA, USA

    Yinin Hu MD, Emily J. White BA & Craig L. Slingluff Jr MD

  2. Department of Public Health Sciences, University of Virginia Health System, Charlottesville, VA, USA

    Mark E. Smolkin MS & Gina R. Petroni Ph.D

  3. Cancer Center, University of Virginia Health System, Charlottesville, VA, USA

    Patrice Y. Neese NP

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  1. Yinin Hu MD
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Correspondence to Yinin Hu MD.

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Hu, Y., Smolkin, M.E., White, E.J. et al. Inflammatory Adverse Events are Associated with Disease-Free Survival after Vaccine Therapy among Patients with Melanoma. Ann Surg Oncol 21, 3978–3984 (2014). https://doi.org/10.1245/s10434-014-3794-3

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  • DOI: https://doi.org/10.1245/s10434-014-3794-3

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