Date of Award

January 2016

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Jennifer Choi

Second Advisor

Marcus Bosenberg

Abstract

Novel immunotherapies for oncologic treatment include anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) agents. These therapies activate the body’s inherent immune response against tumor cells by stimulating T cell proliferation. With the recent approval of agents such as nivolumab and pembrolizumab for the treatment of melanoma, lung cancer, and renal cell cancer, there is a growing need to better characterize their toxicity profiles. This study sought to provide a clinical and histologic description of the cutaneous toxicities seen in patients receiving anti-PD-1/PD- L1 treatment. Cases of patients on anti-PD-1/PD-L1 therapy who developed cutaneous adverse effects were collected from a single tertiary care hospital from 2010 to 2015. Data regarding demographics of patients, concurrent medications, therapeutic regimen, clinical morphology of cutaneous lesions, and tumor response were collected. A total of 20 patients were included in the study, with the majority of patients being treated with nivolumab alone. The majority of cases had a clinical morphology consisting of erythematous papules with scale in a variety of distributions and associated pruritus. Most cases were treated with topical corticosteroids and did not require discontinuation of oncologic treatment. Out of six patients with lung cancer who were treated with an anti-PD-1/PD-L1 agent alone, five patients (83%) responded to treatment. Nearly all cases for which biopsies were available (16 of 17 cases, 94%) showed features of lichenoid interface dermatitis. In addition, 47% of the cases (8 of 17) showed features of spongiotic dermatitis. These results support a cutaneous reaction associated with anti-PD- 1/PD-L1 therapies that has distinct clinical and histologic features.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 08/24/2018

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