# Case report: Immune checkpoint inhibitor-induced fulminant diabetic ketoacidosis: a case-based review and considerations for immunotherapy discontinuation

## TL;DR

A lung cancer patient with specific mutations experienced life-threatening diabetes after immunotherapy, showing both benefits and risks of the treatment.

## Contribution

Highlights a rare but fatal endocrine complication of immune checkpoint inhibitors in cancer patients with specific mutations.

## Key findings

- ICI therapy provided sustained disease stability and symptom improvement in a patient with LUAD and KRAS/TP53 mutations.
- The patient developed fulminant diabetic ketoacidosis, a severe immune-related adverse event, leading to multi-organ failure and death.
- The case underscores the need for long-term metabolic monitoring during immunotherapy, regardless of treatment duration or imaging results.

## Abstract

To report a case of advanced lung adenocarcinoma (LUAD) harboring KRAS p.G12C and TP53 p.R273C mutations. While immune checkpoint inhibitor (ICI) therapy offered remarkable clinical benefits, it concurrently induced a fatal endocrine complication, highlighting the dual-natured impact of immunotherapy.

An elderly male diagnosed with Stage IV LUAD achieved sustained stable disease (SD) and symptomatic improvement through a sequential therapeutic strategy, including platinum-based chemotherapy followed by the PD-1 inhibitor sintilimab combined with anti-angiogenic agents (apatinib or anlotinib). However, the patient developed severe coma, hyperglycemia and metabolic disorder. Laboratory investigations confirmed fulminant ICI-related diabetic ketoacidosis (DKA). Despite intensive resuscitative efforts, the patient succumbed to multi-organ failure.

This case demonstrates that while ICIs can provide exceptional long-term benefits in advanced NSCLC, particularly in patients with highly immunogenic mutation profiles, they may also trigger late-onset fatal irAEs. Our findings underscore the imperative for close, long-term metabolic surveillance throughout the course of immunotherapy, regardless of treatment duration or radiological stability.