Pembrolizumab
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Various toxicities: case report A 76-year-old man developed immune-mediated hypophysitis with adrenocorticotropic hormone (ACTH) deficiency, peripheral hypothyroidism, immune-mediated hepatic cytolysis and collagenous colitis during treatment with pembrolizumab for cutaneous melanoma. The man, who had a stage IV multimetastatic cutaneous melanoma, started receiving treatment with pembrolizumab [route and dosage not stated]. He had a prolonged and near-complete response for 14 months. About 2 months after initiating treatment, the use of PD-1 inhibitor pembrolizumab was complicated by both grade 2 immune-mediated hypophysitis with ACTH deficiency, as well as peripheral hypothyroidism. Approximately 9 months after the introduction of pembrolizumab, grade 2 immune-mediated hepatic cytolysis emerged, which resolved spontaneously and did not contraindicate the continuation of treatment after a temporary interruption to perform liver tests. Fourteen months after the initiation of therapy, he presented with an episode of grade 3 diarrhoea (up to 9 watery non-mucous or bloody stools/day), complicated by asymptomatic hypokalaemia, with no signs showing in an electrocardiogram, necessitating however an intravenous potassium replacement. The rectosigmoidoscopy revealed colonic diffuse congestion without ulceration. During endoscopy, systematic biopsies were performed. Histologically, the fragments analysed showed a moderately thickened subepithelial collagen layer associated with a mild mixed inflammatory infiltrate within the lamina propria, with the presence of lymphocytes and plasma cells. There was no was no increase in the number of intraepithelial lymphocytes with approximately 5–10% intraepithelial lymphocytes. There were no ulcerations, granuloma lesions or viral inclusion bodies. Based on this, a diagnosis of collagenous colitis was considered. The man’s pembrolizumab therapy was temporally interrupted, and he was successfully treated with prednisone. However, during prednisone tapering, he had a recurrence of diarrhoea. The treatment was changed to budesonide, resulting in a definitive and complete resolution of the diarrhoea. At the time of the report, budesonide had been discontinued and pembrolizumab had not been restarted. He showed a bone progression, which was treated by radiotherapy alone [not all outcomes stated]. Calvani J, et al. An unusual digestive complication under anti-PD-1 (pembrolizumab). Annales de Pathologie 40: 320-323, No. 4, Jul 2020. Available from: URL: http:// 803497191 doi.org/10.1016/j.annpat.2020.02.001 [French; summarised from a translation]
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Reactions 22 Aug 2020 No. 1818
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