A case of pembrolizumab-induced type-1 diabetes mellitus and discussion of immune checkpoint inhibitor-induced type 1 diabetes

Abstract

Immune checkpoint inhibitors such as pembrolizumab, ipilimumab, and nivolumab, now FDA-approved for use in treating several types of cancer, have been associated with immune-related adverse effects. Specifically, the antibodies targeting the programmed-cell death-1 immune checkpoint, pembrolizumab and nivolumab, have been rarely reported to induce the development of type 1 diabetes mellitus. Here we describe a case of a patient who developed antibody-positive type 1 diabetes mellitus following treatment with pembrolizumab in combination with systemic chemotherapy for metastatic adenocarcinoma of the lung. We will also provide a brief literature review of other rarely reported cases of type 1 diabetes presenting after treatment with pembrolizumab and nivolumab, as well as discussion regarding potential mechanisms of this adverse effect and its importance as these drugs continue to become even more widespread.

Keywords: Diabetes mellitus; Immune-related adverse effect; Immunomodulatory; Ipilimumab; Nivolumab; Pembrolizumab.

Fig. 1

Blood glucose and c-peptide levels were measured throughout treatment with pembrolizumab, nab-paclitaxel, and carboplatin for adenocarcinoma of the lung. The data points represent 7-day intervals. Treatment was delayed several times for cytopenias, in addition to hyperglycemia after C2D1. C4D8 was held completely for cytopenias. C cycle, D day, P pembrolizumab, N nab-paclitaxel, R carboplatin, Anti-GAD anti-glutamic acid decarboxylase, Anti-IA2 anti-islet antigen 2

Fig. 2

Pre- (i) and post-treatment (ii) chest computed tomography (CT) scans demonstrating an overall decrease in size of the patient’s right upper and right lower lobe nodules after 4 cycles of treatment with pembrolizumab, nab-paclitaxel, and carboplatin. Interval between pre- and post-treatment scans was approximately 5 months. a Pre-treatment CT scan with a lobular, partially spiculated peripheral right upper lobe nodule, measuring 13 mm in the long axis. Resolved on post-treatment scan. b Pre-treatment CT scan with a lobular, partially spiculated right upper lobe nodule, measuring 10 mm in the long axis. Resolved on post-treatment scan. c Pre-treatment CT scan with a well-circumscribed right lower lobe peripheral nodule, measuring 15 mm in the long axis. Resolved on post-treatment scan