Pembrolizumab-induced fulminant type 1 diabetes mellitus: a case report and literature review

As pembrolizumab has been widely used in the immunotherapy of various solid tumors such as melanoma and lung cancer, reports of pembrolizumab-related adverse drug events have gradually attracted attention; however, cases of pembrolizumab-induced fulminant type 1 diabetes mellitus (FT1DM) remain rare. This article reports a case of a young male patient with clear cell renal cell carcinoma (ccRCC) and suspected pulmonary metastases, who had a prior history of hypothyroidism and no family history of diabetes. After 22 cycles of pembrolizumab treatment, the patient developed lethargy and marked metabolic acidosis. The patient had markedly elevated blood glucose with an HbA1c of 6.7% and extremely low C-peptide levels. Given the history of pembrolizumab treatment, the patient was diagnosed with immune checkpoint inhibitor-associated FT1DM. His condition improved after fluid resuscitation and insulin therapy, and he was subsequently discharged. The patient continued treatment with the same agent for another three cycles before permanent discontinuation. Given the rarity of pembrolizumab-associated FT1DM, we further reviewed the literature. A literature search identified 32 confirmed cases of pembrolizumab-associated FT1DM, which were included in the analysis. The 32 reported cases mainly involved lung cancer and melanoma, with FT1DM onset ranging from 1 to 24 treatment cycles. GADA-positive patients tended to develop FT1DM earlier. Thyroid dysfunction occurred before or concurrently with FT1DM in 90% of cases. One case of pituitary dysfunction and one case of adrenal dysfunction both occurred after FT1DM onset. These findings suggest that metabolic monitoring should continue throughout pembrolizumab therapy, and that subsequent endocrine dysfunction should be monitored after FT1DM. Pembrolizumab-associated FT1DM requires long-term insulin therapy. Whether to continue or resume pembrolizumab should be decided individually after DKA resolution and glycemic stabilization.