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Immune-related adverse events correlate with improved survival in patients undergoing anti-PD1 immunotherapy for metastatic melanoma

Abstract

Background

Therapeutic chances for metastatic melanoma have consistently changed over the last years with the advent of antibodies targeting the programmed cell death protein-1 (PD-1). Onset of immune-related adverse events (irAEs) during treatment can be a source of concern, and the association with survival outcome is yet to be defined.

Patients and methods

Data of consecutive patients treated with anti-PD1 (nivolumab or pembrolizumab) for metastatic melanoma between July 2013 and January 2018 were retrospectively reviewed. Baseline factors, together with onset of irAEs and vitiligo during treatment, were evaluated to identify predictors of progression-free (PFS) and overall (OS) survival. PFS and OS were assessed using Kaplan–Meier and Cox models.

Results

Overall, 173 patients were included in the present analysis, and 102 patients (59%) experienced irAEs. Disease control rate was 51%. Median (interquartile range) PFS and OS were 4.9 (2.6–13.3) and 8.6 (3.5–18.3) months, respectively. At multivariate analysis, irAEs occurrence was independently associated with improved PFS [HR 0.47 (95% CI 0.26, 0.86); p = 0.016], and correlated with better OS [HR 0.39 (95% CI 0.18, 0.81); p = 0.007]. Among various irAEs, the occurrence of vitiligo was associated with a trend toward a non-significant improved OS in comparison with other irAEs (p = 0.061). Median OS was undefined for patients experiencing vitiligo vs. 21.9 months for patients with other irAEs vs. 9.7 months for patients who had no irAEs (p = 0.003).

Conclusions

Our study underlines the association between irAEs and survival outcomes from anti-PD1 therapy. Careful management of treatment-related toxicity can lead to achieve maximum clinical benefit from this therapy.

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Funding

No fundings were received for the present investigation.

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Correspondence to Alice Indini.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Indini, A., Di Guardo, L., Cimminiello, C. et al. Immune-related adverse events correlate with improved survival in patients undergoing anti-PD1 immunotherapy for metastatic melanoma. J Cancer Res Clin Oncol 145, 511–521 (2019). https://doi.org/10.1007/s00432-018-2819-x

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  • DOI: https://doi.org/10.1007/s00432-018-2819-x

Keywords

  • Melanoma
  • Immunotherapy
  • Anti-PD1
  • IrAEs
  • Vitiligo
  • Toxicity