Recovery from insulin dependence in immune checkpoint inhibitor‐associated diabetes mellitus: A case report

Abstract

Immune checkpoint inhibitor‐associated diabetes mellitus (ICI‐DM) is a rare immune‐related adverse event and is usually considered permanent. Here, we report the first case of a 54‐year‐old man with ICI‐DM who recovered from insulin dependence. He was diagnosed with lung cancer and started pembrolizumab therapy. After seven cycles, he developed ICI‐associated secondary adrenal insufficiency and started hydrocortisone supplementation. Subsequently, he complained of fatigue, and blood examinations showed hyperglycemia with ketosis. A glucagon challenge test indicated insulin dependence. He was diagnosed with ICI‐DM and insulin therapy was initiated. Pembrolizumab therapy was discontinued due to concomitant ICI‐associated hepatitis. Six months later, a glucagon challenge test result showed an improvement in insulin secretion, and insulin therapy was discontinued. The lung cancer lesions continued to shrink. Even if ICI‐DM develops, it might be possible to control the underlying cancer while avoiding lifelong insulin therapy through early discontinuation of ICI.

Reaching the Diagnosis of Checkpoint Inhibitor-Induced Diabetes Mellitus in Different Clinical Scenarios: A Real-World Application of Updated Diagnostic Criteria

“…Once the diagnosis of CPI-DM is confirmed, a multiple insulin injection regimen is recommended as the firstline treatment. CPI-DM is considered permanent, requiring lifelong insulin replacement, but a single case of remission has also been described in the literature [39]. Glucocorticoids are not recommended due to their uncertain efficacy and potential worsening of hyperglycemia [5].…”

A Concerted Vision to Advance the Knowledge of Diabetes Mellitus Related to Immune Checkpoint Inhibitors

“…The prevailing explanation of this chronicity considers irDM as "burnout" toxicity featuring irreversible damage, while most irAEs are considered "smouldering toxicities", featured by off-target T-cell activation that waxes and wanes, resolving after administration of steroids or ICPi withdrawal or both interventions [10,18]. However, exceptionally rare cases of reversible irDM have been reported [104,121], rendering the monitoring essential to avert a deleterious continuation of unnecessary insulin therapy. Second, the monitoring will help to better assess the riskreward ratio for the resumption of ICPi treatment that was withdrawn due to severe irDM, called ICPi rechallenge [122][123][124].…”