scholarly journals Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor‐induced diabetes mellitus: A report of two cases

2021 ◽  
Vol 9 (9) ◽  
Author(s):  
Noriko Fujiwara ◽  
Mayu Watanabe ◽  
Akihiro Katayama ◽  
Yohei Noda ◽  
Jun Eguchi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Longitudinal Observation ◽  
Before And After

A Systematic Review of Cases of Diabetes Mellitus following Immune Checkpoint Inhibitor Therapy for Cancer

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 204-LB ◽  
Author(s):  
KARA R. MIZOKAMI-STOUT ◽  
ROMA GIANCHANDANI ◽  
MARK MACEACHERN ◽  
RAVI M. IYENGAR ◽  
SARAH YENTZ ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy

scholarly journals A COMMON PITUITARY AUTOANTIBODY IN TWO PATIENTS WITH IMMUNE CHECKPOINT INHIBITOR-MEDIATED HYPOPHYSITIS: ZCCHC8

2020 ◽  
Vol 6 (4) ◽  
pp. e151-e160
Author(s):  
Amanda Leiter ◽  
Sacha Gnjatic ◽  
Mary Fowkes ◽  
Seunghee Kim-Schulze ◽  
Ilaria Laface ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Severe Fatigue ◽  
Metastatic Urothelial Cancer ◽  
Before And After ◽  
Serial Samples ◽  
First Time

Objective: Hypophysitis is an increasingly recognized adverse effect of immune checkpoint inhibitor (ICI) therapy for malignancy. However, the mechanisms through which ICIs induce hypophysitis are largely unknown. We aim to describe 2 cases of ICI-mediated hypophysitis and perform autoantibody profiling on serial samples from these patients to determine if common autoantibodies could be identified. Methods: We describe 2 cases of patients with metastatic urothelial cancer who received ICI therapy and subsequently developed severe fatigue, prompting a hormonal workup consistent with hypopituitarism. Patient 1 received the ICI ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4) and patient 2 received the ICI pembrolizumab (anti-programmed cell death protein 1). Both patients had serial seromic immune biomarker profiling using high-density protein arrays before and after developing hypophysitis. Once a common autoantibody was found, zinc finger CCHC-type containing 8 (ZCCHC8), we used immunohistochemistry to assess its presence in pituitary tissue. Results: Of a limited number of increased autoantibodies detected, those to ZCCHC8 were the only common antibodies to increase at least 3-fold post-hypophysitis in both patients. Using immunohistochemistry staining, we show for the first time that ZCCHC8 is expressed in pituitary gland tissue. Conclusion: Seromic profiling identified a common autoantibody, ZCCHC8, in 2 patients who developed hypophysitis on ICI therapy, and other serial autoantibody increases in each patient. These findings warrant validation in other cohorts to determine if the response is to self or tumor antigen, and may reveal novel insights into pituitary gland physiology and the pathogenesis of ICI-mediated hypophysitis.

scholarly journals Immune Checkpoint Inhibitor-Associated Diabetes Mellitus: A Single-Institution Experience

2020 ◽  
Author(s):  
David J. Byun ◽  
Rebecca Braunstein ◽  
Jessica Flynn ◽  
Junting Zheng ◽  
Robert A. Lefkowitz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Case Series ◽  
Retrospective Chart Review ◽  
Single Institution ◽  
Pancreatic Atrophy ◽  
Gad65 Autoantibodies ◽  
Design And Methods

<b>OBJECTIVE</b> <p>To characterize immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) in a single-institution case series. </p> <p><b>DESIGN AND METHODS</b></p> <p>Retrospective chart review of 18 patients with new-onset ICI-DM following anti-PD-1/anti-PD-L1 therapy for advanced carcinomas.</p> <p><b>RESULTS</b></p> <p>9/18 patients had diabetic ketoacidosis (median glucose: 27.92mmol/L; median glucose before presentation: 6.35mmol/L). Median C-peptide at ICI-DM diagnosis was low, and declined during follow-up. Median anti-PD-1/anti-PD-L1 duration before ICI-DM was 3.65 months (range 0.56-12.23). Time to ICI-DM onset was a median 1.4 months/3 ICI cycles and 6 months/10 cycles in those positive and negative for GAD65 autoantibodies, respectively. Time to ICI-DM onset was a median 2.5 months/3 ICI cycles and 4.8 months/8 cycles after anti-PD-L1 or anti-PD-1 therapy, respectively. Significant pancreatic atrophy was seen radiographically.</p> <p><b>CONCLUSIONS</b></p> <p>ICI-DM presents abruptly, appears irreversible, is characterized by pancreatic atrophy, and may <a>occur both earlier following PD-L1 blockade compared to PD-1 inhibition </a>and in those who have positive GAD65 autoantibodies.</p>

A case series of immune checkpoint inhibitor induced diabetes mellitus (ICI-DM).

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e22080-e22080
Author(s):  
Venessa H Tsang ◽  
Roderick J Clifton-Bligh ◽  
Georgina V. Long ◽  
Alexander David Guminski ◽  
Alexander M. Menzies
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Case Series

scholarly journals Combined immune checkpoint inhibitor therapy with nivolumab and ipilimumab causing acute-onset type 1 diabetes mellitus following a single administration: two case reports

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Marco Zezza ◽  
Christophe Kosinski ◽  
Carine Mekoguem ◽  
Laura Marino ◽  
Haithem Chtioui ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Acute Onset ◽  
Single Administration

Abstract Background The use of immune checkpoint inhibitor (ICI) therapy is becoming a standard of care for several cancers. Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand (PD-L1) cause a broad spectrum of autoimmune adverse events. ICI-induced type 1 diabetes mellitus (T1DM) is extremely rare (< 1%) but potentially life-threatening. It appears to be more common with PD-1 blockade (or combination immunotherapy) than with anti-CTLA-4 therapy, often during the first three to six months of therapy. Cases presentation We report an acute onset T1DM with severe inaugural diabetic ketoacidosis (DKA) and remarkably elevated Glutamic Acid Decarboxylase antibody (GADA) titres following a single administration of combined ICI therapy with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) in two adult patients with advanced metastatic melanoma. In these cases, the time to diabetes onset was remarkably short (two and five weeks), and one presented with fulminous T1DM in a previous long-standing type 2 diabetes mellitus. Conclusions Oncological patients treated with combination therapy of anti-PD-1 and anti-CTLA-4 can develop a particular pattern of T1DM, with very rapid onset within a few weeks after starting ICI therapy, even in the presence of an existing type 2 diabetes. ICI-induced T1DM is a medical emergency in presence of severe inaugural DKA and requires a collaboration between specialists and primary care physicians, as well as patient education, for early diagnosis and supportive care.

Sign in / Sign up

Export Citation Format

Share Document