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=> array:1 [ "titulo" => "Diabetes mellitus autoinmune inducida por avelumab" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Avelumab is an immune checkpoint inhibitor (ICI) indicated for the treatment of patients with locally advanced or metastatic Merkel cell carcinoma and renal or urothelial carcinoma.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> ICIs increase the immune response against cancer cells by activating cytotoxic T-cells, and although rare, all ICIs can cause autoimmune adverse effects. If activated T-cells infiltrate the pancreas, they destroy its beta cells and lead to type 1 diabetes mellitus.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a patient who developed autoimmune diabetes mellitus eight weeks after receiving the first dose of avelumab.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A 67-year-old male, with a history of robotic radical prostatectomy for acinar adenocarcinoma in January 2022. The abdominal computed axial tomography (CAT) scan performed in November 2022 revealed a solid tumour measuring 27 × 38 mm in the posterior leaflet of the lower pole of the right kidney, and urothelial thickening hyperenhancement at the level of the upper calyx and left renal pelvis. Partial right nephrectomy was performed in January 2023, with a pathological diagnosis of adenocarcinoma, and left nephrectomy in March 2023 with a histological diagnosis of urothelial carcinoma (UC) of the renal pelvis, stage IV, T3 N2M0. On 6 April 2023, he received the first chemotherapy cycle of the cisplatin and gemcitabine (CisGem) regimen, and eight cycles were completed, ending on 18 July 2023. When a new abdominal CT scan showed that the locally advanced UC had not progressed with the previous chemotherapy, immunotherapy with avelumab monotherapy at a dose of 800 mg by intravenous infusion every two weeks was indicated, with the first dose received on 25 August, followed by 15 and 29 September and 13 October 2023. On 27 October, a blood glucose level of 338 mg/dL was recorded. Reported polyuria and polydipsia. Avelumab was discontinued and the patient was referred to the emergency department. On physical examination: height 181 cm, weight 63 kg. Good general condition; creatinine 1.8 mg/dL, sodium (Na) 125 mEq/L, potassium (K) 5 mEq/L, venous blood gases: Ph 7.3, HCO3 29 mmol/L, EB 1.4 mmol/L. He was treated with rapid insulin and discharged on insulin glargine and repaglinide. As high blood glucose levels persisted, the patient was referred to the Diabetes Unit. Repaglinide was discontinued and insulin glargine and multiple doses of insulin lispro were started. Anti-glutamic acid (anti-GAD) and anti-pancreatic islet antibodies negative. Basal C-peptide: <0.1 ng/mL (normal value 0.8–3.9) and haemoglobin A1c 8.6%.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The first case of diabetes mellitus induced by the combination of avelumab and utomilumab was reported in 2018,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and in 2019 another case in avelumab monotherapy.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The incidence of diabetes mellitus in patients treated with ICIs is rare, about 1%. Unlike conventional type 1 diabetes mellitus, ICI-induced diabetes mellitus is characterised by severe and persistent insulin deficiency since diagnosis, evidenced by very low or absent C-peptide levels, leading to diabetic ketoacidosis if not promptly treated with insulin. It occurs between seven and 17 weeks after the start of immunotherapy, with very high blood glucose levels and difficult metabolic control. Haemoglobin A1c is usually not very high at diagnosis due to the rapid onset of insulin deficiency, and anti-pancreatic antibodies are often negative.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Knowing about this form of avelumab-induced autoimmune diabetes mellitus is important in order not to delay the initiation of multi-dose insulin therapy, as was the case here. It is also important to emphasise that, once blood glucose levels have stabilised, immunotherapy should be continued if still indicated, as diabetes mellitus is irreversible.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0030" class="elsevierStylePara elsevierViewall">This work has not received any funding.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflict of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Product review: avelumab, an anti-PD-L1 antibody" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.M. Collins" 1 => "J. Gulley" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Human Vaccin Immunother." "fecha" => "2019" "volumen" => "15" "paginaInicial" => "891" "paginaFinal" => "908" "itemHostRev" => array:3 [ "pii" => "S1542356518300065" "estado" => "S300" "issn" => "15423565" ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adverse events associated with immune chekpoint inhibitors: a new era in autoimmune diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H.K. Akturk" 1 => "A.W. Michels" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MED.0000000000000546" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Endocrinol Diabetes Obes." "fecha" => "2020" "volumen" => "27" "paginaInicial" => "187" "paginaFinal" => "193" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32618630" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combination avelumab and utomilumab immunotherapy can induce diabetis ketoacidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P.W. Atkins" 1 => "D.M. Thompson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.diabet.2017.05.005" "Revista" => array:6 [ "tituloSerie" => "Diabetes Metab." "fecha" => "2018" "volumen" => "44" "paginaInicial" => "514" "paginaFinal" => "515" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28648834" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Case of fulminant type 1 diabetes induced by the anti-programmed death-ligand 1 antibody, avelumab" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Shibayama" 1 => "H. Kameda" 2 => "S. Ota" 3 => "K. Tsuchida" 4 => "K.Y. Cho" 5 => "A. Nakamura" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jdi.13022" "Revista" => array:6 [ "tituloSerie" => "J Diabetes Investig." "fecha" => "2019" "volumen" => "10" "paginaInicial" => "1385" "paginaFinal" => "1387" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30738003" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recent advances in immune chekpoint inhibitor-induced type 1 diabetes mellitus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D. Liao" 1 => "C. Liu" 2 => "S. Chen" 3 => "F. Liu" 4 => "D. Shangguan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Int Immunopharmacol." 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Journal Information
Vol. 162. Issue 12.
Pages 617-618 (June 2024)
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Vol. 162. Issue 12.
Pages 617-618 (June 2024)
Letter to the Editor
Avelumab-induced autoimmune diabetes mellitus
Diabetes mellitus autoinmune inducida por avelumab
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