Dual checkpoint inhibitor-associated eosinophilic enteritis

J Yang,J Yang,S M Lagana,Y M Saenger,Y M Saenger,R D Carvajal,R D Carvajal

doi:10.1186/s40425-019-0743-5

Abstract

BackgroundEosinophilia has been reported as a rare, new biological effect of immune checkpoint inhibition that may be associated with improved treatment response and the development of immune-related adverse events.Case presentationWe report a case of dual checkpoint inhibitor-associated hypereosinophilia and eosinophilic enteritis in a patient with advanced cutaneous melanoma. Rapid resolution of peripheral eosinophilia and associated symptoms was achieved with steroids alone.ConclusionsImmune checkpoint inhibition can trigger inflammation in virtually any organ in the body, leading to diverse clinical manifestations. To our knowledge, this is the first case report of eosinophilic enteritis due to ipilimumab plus nivolumab.

Highlights

Immune checkpoint inhibition with anti-PD-1 and anti-CLTA-4 agents has revolutionized the treatment of various cancers, but can be associated with a diverse range of immune-related adverse events including pneumonitis, colitis, and rare cases of myocarditis
Restaging scans on 8/27/ 2018 showed further disease progression in the liver and the development of a new soft tissue paraspinal lesion. He was evaluated by a gastroenterologist and underwent an upper endoscopy which revealed no gross abnormalities, but biopsy of the duodenum revealed a prominent eosinophilic infiltrate (80–100 eosinophils per high power field (HPF)) consistent with eosinophilic enteritis (Fig. 2)
Transcriptomic analysis of gastric biopsies obtained from patients with eosinophilic gastroenteritis reveals activation of the Th2 cytokine signaling pathways IL-4, IL-5, and IL-13

Summary

Introduction

Immune checkpoint inhibition with anti-PD-1 (programmed death 1) and anti-CLTA-4 (cytotoxic Tlymphocyte associated protein 4) agents has revolutionized the treatment of various cancers, but can be associated with a diverse range of immune-related adverse events including pneumonitis, colitis, and rare cases of myocarditis. (AEC) of 700/mm3 [normal range 30–350; peripheral eosinophilia defined as AEC > 500/mm3] (Fig. 1) He received 2 additional doses of ipilimumab plus nivolumab on 7/12/2018 and 8/1/2018 with concurrent stereotactic body radiation therapy (SBRT) to 2 liver lesions (50 Gy over 5 fractions to each lesion). Restaging scans on 8/27/ 2018 showed further disease progression in the liver and the development of a new soft tissue paraspinal lesion He was evaluated by a gastroenterologist and underwent an upper endoscopy which revealed no gross abnormalities, but biopsy of the duodenum revealed a prominent eosinophilic infiltrate (80–100 eosinophils per HPF) consistent with eosinophilic enteritis (Fig. 2). Most recent imaging showed disease progression in the lung, and he was restarted on ipilimumab plus nivolumab in combination with T-VEC injections

Discussion

Findings

Conclusion