A41-22 Immune Checkpoint Inhibitor (ICI) Toxicity Overlap: The Challenge of Treating Pneumonitis in a Patient With ICI Induced Diabetes

Abstract Introduction Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignancies by enhancing antitumor immune activity. However, these therapies are associated with a broad spectrum of immune-related adverse events (irAEs) that can affect virtually any organ system. While individual irAEs are well characterized, concomitant or sequential irAEs present unique therapeutic challenges—particularly when treatment of one toxicity exacerbates another. Case Presentation A 52-year-old male with a history of hepatitis B infection and hepatocellular carcinoma (HCC) treated with hepatic artery embolization was started on STRIDE regimen ICI therapy (tremelimumab and durvalumab) for Child-Pugh A-5 stage IV HCC. Following the first cycle, he developed immune-mediated hepatitis requiring high-dose corticosteroids and mycophenolate mofetil (MMF), after which his liver function normalized and immunotherapy was resumed. He subsequently tolerated nine cycles of durvalumab before presenting with new-onset hyperglycemia. Laboratory evaluation revealed a random glucose of 300 mg/dL, HbA1c of 6.7%, low C-peptide, and negative glutamic acid decarboxylase antibodies—findings consistent with ICI-induced insulin-dependent diabetes mellitus. Durvalumab was discontinued, and insulin therapy was initiated. Shortly thereafter, the patient developed cough, dyspnea, and new oxygen dependence. Chest computed tomography demonstrated bilateral upper-lobe ground glass opacities as well as dense peribronchovascular nodular and peripheral consolidations. Infectious causes were excluded, and the imaging pattern was consistent with organizing pneumonia secondary to grade 3 ICI-induced pneumonitis. High-dose prednisone (1 mg/kg) led to clinical improvement; however, steroid therapy significantly worsened his glycemic control, necessitating escalating insulin doses. To balance immune suppression and metabolic control, a rapid steroid taper was pursued with simultaneous initiation of MMF as a steroid-sparing agent. The patient continues to demonstrate clinical improvement under close multidisciplinary follow-up with pulmonology, endocrinology, and oncology. Discussion This case highlights the complex management of overlapping ICI toxicities—specifically, pneumonitis and insulin-dependent diabetes mellitus. Corticosteroids remain the cornerstone of pneumonitis management. Literature on the use of other immunosuppressants, including MMF, infliximab, or intravenous immunoglobulin for steroid-refractory pneumonitis or as steroid-sparing therapy, remains limited. As seen in our case, steroids can precipitate severe hyperglycemia and increase the risk of diabetic ketoacidosis in patients with ICI-induced diabetes. Conversely, premature steroid tapering raises the risk of pneumonitis recurrence. Evidence-based strategies for managing concurrent irAEs are lacking. This case underscores the necessity of individualized, multidisciplinary care and vigilant monitoring to balance immune suppression, metabolic stability, and oncologic outcomes in patients with complex ICI toxicities. This abstract is funded by: None