Original article
Survival and prognosis of individuals receiving programmed cell death 1 inhibitor with and without immunologic cutaneous adverse events

https://doi.org/10.1016/j.jaad.2019.06.035Get rights and content

Background

The treatment response to new immunotherapy in advanced melanoma patients remains varied between individuals. Immune-related cutaneous side effects might have prognostic value.

Objective

To determine whether development of ≥1 of the 3 immune-mediated cutaneous events (eczema, lichenoid reaction, or vitiligo-like depigmentation) is associated with improved progression-free survival.

Methods

A cohort study of adults with stage IIIC-IV melanoma treated with pembrolizumab or nivolumab during May 1, 2012-February 1, 2018, at Westmead Hospital, Sydney, Australia. Treatment response was based on iRECIST version 1.1.

Results

In total, 82 patients of an average age of 59.9 years were included. Median follow-up was 40.7 months; 33 patients had ≥1 target skin reaction. Skin reactions developed in one-third of individuals by 6 months. At any given time, the instantaneous risk of disease progression and death was lower for individuals who had ≥1 cutaneous adverse event (CAE) develop. Compared with individuals with no CAE, the hazard ratio for disease progression and death for individuals who had ≥1 CAE develop was 0.46 (95% confidence interval 0.23-0.91; P = .025) by the time-dependent Cox proportional hazards model.

Limitations

Single-center study.

Conclusion

This study demonstrates an association between the development of ≥1 of 3 CAEs and improved progression-free survival in this cohort of patients.

Section snippets

Study design

This was a prospective study of adults with unresectable stage IIIC-IV metastatic melanoma treated with PD-1 (pembrolizumab and nivolumab) at or above the Food and Drug Administration–approved doses during May 1, 2012-February 1, 2018, at Westmead Hospital, Sydney, Australia. All patients were part of a clinical trial or receiving therapy on compassionate grounds. The study was approved by the Westmead Hospital Human Research Ethics Committees (HERC LNR/13/WMEAD/418). All patients received ≥1

Patient characteristics

A total of 82 patients were included in this study; 5 patients received nivolumab and 77 pembrolizumab. The mean age was 59.9 (standard deviation 12.7, range 19-82) years, and 51 (62%) patients were men (Table I). The median follow-up duration was 40.7 months, with the maximum being 47.3 months.

The incidence of eczema, lichenoid reaction, and vitiligo-like depigmentation

During the follow-up period, 33 patients had ≥1 of the 3 skin reactions of interest (Fig 1). Approximately one-third of these individuals (n = 10) also experienced a second skin reaction, and 2 patients

Discussion

This current study builds upon the previously published data by Hwang et al at the same institution.11 The extended period of observation and follow-up was included in this study. The previous study identified that the 3 most common immune-related adverse events among patients receiving PD-1 treatment were lichenoid reactions, eczema, and vitiligo-like depigmentation. It is generally accepted that all 3 conditions are mediated by lymphocyte damage.1, 11, 14, 19

Dermatitis has been proposed as a

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  • Cited by (0)

    Ms Chan and Ms Hwang contributed equally in this study.

    Funding sources: None.

    Conflicts of interest: None disclosed.

    Reprints not available from the authors.

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