Journal of Cancer Research and Clinical Oncology

, Volume 145, Issue 2, pp 511–521 | Cite as

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

  • Alice IndiniEmail author
  • Lorenza Di Guardo
  • Carolina Cimminiello
  • Michele Prisciandaro
  • Giovanni Randon
  • Filippo De Braud
  • Michele Del Vecchio
Original Article – Clinical Oncology



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.


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).


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.


Melanoma Immunotherapy Anti-PD1 IrAEs Vitiligo Toxicity 



No fundings were received for the present investigation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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.

Human rights and animal participants

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

Informed consent

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

Supplementary material

432_2018_2819_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Melanoma Medical Oncology Unit, Department of Medical Oncology and HematologyFondazione IRCCS Istituto Nazionale dei Tumori di MilanoMilanItaly
  2. 2.Department of Medical Oncology and HematologyFondazione IRCCS Istituto Nazionale dei Tumori di MilanoMilanItaly
  3. 3.Università degli studi di MilanoFondazione IRCCS Istituto Nazionale dei Tumori di MilanoMilanItaly

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