1672-P: Characterization of Immune Checkpoint Inhibitor–Mediated Hyperglycemia: Beyond Insulin-Dependent Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1672-P
Author(s):  
AMANDA LEITER ◽  
EMILY CARROLL ◽  
DANIELLE C. BROOKS ◽  
JENNIFER BEN SHIMOL ◽  
ELLIOT EISENBERG ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Insulin Dependent Diabetes ◽  
Insulin Dependent

scholarly journals CANDIED: A Pan-Canadian Cohort of Immune Checkpoint Inhibitor-Induced Insulin-Dependent Diabetes Mellitus

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 89
Author(s):  
Thiago P. Muniz ◽  
Daniel V. Araujo ◽  
Kerry J. Savage ◽  
Tina Cheng ◽  
Moumita Saha ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Insulin Dependent Diabetes Mellitus ◽  
High Response Rate ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent

Immune checkpoint inhibitor (ICI)-induced insulin-dependent diabetes mellitus (IDDM) is a rare but potentially fatal immune-related adverse event (irAE). In this multicentre retrospective cohort study, we describe the characteristics of ICI-induced IDDM in patients treated across five Canadian cancer centres, as well as their tumor response rates and survival. In 34 patients identified, 25 (74%) were male and 19 (56%) had melanoma. All patients received anti-programed death 1 (anti-PD1) or anti-programmed death ligand-1 (anti-PD-L1)-based therapy. From ICI initiation, median time to onset of IDDM was 2.4 months (95% CI 1.1–3.6). Patients treated with anti-PD1/PD-L1 in combination with an anti-cytotoxic T lymphocyte antigen 4 antibody developed IDDM earlier compared with patients on monotherapy (1.4 vs. 3.9 months, p = 0.05). Diabetic ketoacidosis occurred in 21 (62%) patients. Amongst 30 patients evaluable for response, 10 (33%) had a complete response and another 10 (33%) had a partial response. Median overall survival was not reached (95% CI NE; median follow-up 31.7 months). All patients remained insulin-dependent at the end of follow-up. We observed that ICI-induced IDDM is an irreversible irAE and may be associated with a high response rate and prolonged survival.

Abstract LB-060: Characterization of the immune checkpoint inhibitor response in the MC38 murine colon cancer model

2019 ◽  
Author(s):  
Patrick Fadden ◽  
Thi Bui ◽  
David Hurtado ◽  
Kelli Davis ◽  
Ian Belle ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Cancer Model ◽  
Murine Colon

scholarly journals Histopathologic Characterization of Myocarditis Associated With Immune Checkpoint Inhibitor Therapy

2020 ◽  
Vol 144 (11) ◽  
pp. 1392-1396
Author(s):  
Irina Sobol ◽  
Carol L. Chen ◽  
Syed S. Mahmood ◽  
Alain C. Borczuk
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Immune Cell ◽  
Checkpoint Inhibitor ◽  
Case Reports ◽  
Inhibitor Therapy ◽  
Cardiac Complications ◽  
Programmed Death ◽  
Checkpoint Inhibitor Therapy

Context.— Cardiac complications of immune checkpoint inhibitor therapy are rare, but reports of myocarditis are increasing. The findings have been described in case reports as lymphocytic myocarditis, but its histopathology is underreported. Objective.— To review the histology of myocardial biopsy–proven cases of immune checkpoint–associated myocarditis and provide immunohistochemical characterization of the inflammatory infiltrate. Design.— We have encountered 6 patients with biopsy-proven myocarditis in conjunction with therapy using anti–programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) agents with and without cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors and characterized the histopathology and immune cell profile. Results.— The myocarditis was multifocal/diffuse and characterized by a predominant CD163-positive histiocytic infiltrate, with an associated CD8+ and PD-1+ T-lymphocytic infiltrate, some of which were granzyme B positive. Cardiac myocytes showed immunoreactivity for PD-L1 in areas of injury, confirmed using 2 different anti–PD-L1 clones. Four of 6 patients recovered from their cardiac injury. One patient had residual tachycardia-bradycardia syndrome and 1 patient expired. Conclusions.— The diffuse lymphohistiocytic myocarditis associated with this therapy is relatively distinctive, and this diagnosis is strongly suggested based on the histopathologic findings in the correct clinical setting.

scholarly journals MON-LB121 New Onset Insulin Dependent Diabetes Mellitus Secondary to Treatment With Immune Checkpoint Inhibitor

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Syed Rabha Bitat
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent ◽  
New Onset

Abstract Background: Checkpoint inhibitors, immunomodulatory antibodies that are used to enhance the immune system, have substantially improved the prognosis for patients with advanced malignancy like melanoma and lung cancer. Despite important clinical benefits, checkpoint inhibition is associated with a unique spectrum of side effects termed immune-related adverse events (irAEs). IrAEs include dermatologic, gastrointestinal, hepatic, endocrine, and other less common inflammatory events. Among them is endocrine toxicity, most commonly targeting the thyroid, pituitary, or adrenal glands. New-onset diabetes mellitus has been reported in only around 1% of patients in a recent study. Although rare, fulminant and even fatal toxicities may occur with immune checkpoint inhibitors, and therefore, prompt recognition and management is important. Here we are going to present a patient with new onset Insulin dependent Diabetes mellitus secondary to immunotherapy. It usually presents with diabetic ketoacidosis (DKA) and follows a rapid course. Awareness and prompt management are therefore key. History and investigations:62 year old lady diagnosed with Right Uveal melanoma more than 2 years ago and was treated with Enucleation followed by Rt prosthetic eye. Subsequently patient developed metastatic melanoma with subcutaneous lesion in right paravertebral region, right humoral head and right gluteal muscle. It was unclear whether patient had metastatic uveal or cutaneous melanoma. Other PMH includes were Hypertension and Anxiety.Patient was started on Ipilimumab (CTLA-4 inhibitor) and Nivolumab (PD1 inhibitor) 6 months ago, and Ipilimumab was stopped 8 weeks ago due to side effects but continued with Nivolumab. Other current medications were Amlodipine 10 mg once daily and AmitriptylinePatient was complaining of extreme fatigue last one week and was diagnosed with Hypothyroidism with TSH >100 mIU/L (Normal 0.27-4.2) and FT4 5.4 pmol/L (Normal 12.0-22.0), subsequently patient was started on Levothyroxine 50 mcg once daily.Patient presented to emergency department with polyuria and polydipsia last 5 days and also blurred vision for last 3 weeks. Patient did not notice any recent weight loss and had widespread pain, worse on skin lesions and hip joints but did not had any other specific complaints.Patient was current smoker with more than 40 pack year history and was taking 25 units of Alcohol per week for many years. Patient did not had any significant family history including any history diabetes in the family.On examination, patient was clinically dry with capillary refill time was 5 seconds.Investigations showed-Venous blood gas-Blood Glucose - Hi (mmol/L out of range), later 22.7 mmol/LPh- 7.291, PCO2 6.14 kPa, HCO3 19.3 mmol/L, Lactate 2.2 mmol/LBlood ketones- Hi (mmol/L out of range), later >7 mmol/L Other investigations showed-Na 131 mmol/L (Normal 135-145), K 5.4 mmol/L (Normal 3.5-5.1), Urea 7.1 mmol/L (Normal 1.7-8.3)Creatinine 139 umol/L (Normal 49-92)Bilirubin 12 umol/L (Normal 0-20), ALT 56 IU/L (Normal 10-35), ALP 157 IU/L (Normal 35-104)Amylase 59 IU/L (Normal 28-100), Albumin 48 g/L (Normal 34-50), Adjusted Calcium 2.56 mmol/L (Normal 2.2-2.6)9 am Cortisol 826 nmol/L (Normal 133-537), ACTH 28 ng/l (Normal 7.2-63.3)FSH 78.7 IU/L (Normal 25.8-134.8), LH 37.6 IU/L (Normal 7.7-58.5)IGF1 9.6 nmol/L (Normal 3.5-32.0), Prolactin 476 mIU/L (Normal 102-496)HbA1C 10.6% / 93 mmol/mmol (Normal 20-42)Serum Anti-GAD titre- 5 IU/L (Normal 0-10) Patient was started on treatment for Diabetic Ketoacidosis (DKA) with intravenous fluid and also fixed rate Insulin infusion according to protocol. Patient responded well to treatment and biochemical profile improved with initial treatment, subsequently patient was started on regular basal bolus Insulin regime with the help from the diabetes team. Discussion:Here we have presented a case with new onset Insulin dependent Diabetes Mellitus induced by immune checkpoint inhibitor. This kind of Diabetes progress rapidly to severe insulin deficiency compared to spontaneous Type 1 Diabetes, frequently patient present with DKA and do not go into remission. As this condition can develop rapidly, it is suggested that glucose level is to be monitored regularly and also to check HbA1C prior to initiating the immunotherapy. Their management requires complex Insulin regime to get good glycaemic control and add significant comorbidity along with the underlying cancer. The exact pathophysiologic mechanism and predictive biomarkers have not yet been established. The end result is permanent Insulin dependence. In future better characterization and further study is required to improve diagnosis and management, also to follow the natural history of this condition. Reference: 1) Kotwal A, Haddox C, Block M, et alImmune checkpoint inhibitors: an emerging cause of insulin-dependent diabetesBMJ Open Diabetes Research and Care 2019;7:e000591. doi: 10.1136/bmjdrc-2018-000591 2) Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review.de Filette JMK1, Pen JJ2, Decoster L3, Vissers T4, Bravenboer B1, Van der Auwera BJ5, Gorus FK5, Roep BO6,7, Aspeslagh S3, Neyns B3, Velkeniers B1, Kharagjitsingh AV1,

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