Slow progression of type 1 diabetes associated with pembrolizumab and lenvatinib combination therapy in a patient with probable slowly progressive type 1 diabetes mellitus and endometrial cancer.

Abstract

A 58-year-old woman with a body mass index of 26.4 kg/m² was referred because of high glycated hemoglobin (HbA1c) at a medical checkup. Her anti-glutamic acid decarboxylase antibody (GADA) titer was positive (16.0 U/mL; normal < 5.0 U/mL). Her HbA1c was controlled at 6.4%-7.5% using metformin, ipragliflozin, and sitagliptin. Two-and-a-half years later, she was diagnosed with endometrial cancer with pelvic lymph node metastasis and underwent surgery followed by chemotherapy with carboplatin and paclitaxel, then carboplatin and docetaxel. However, owing to enlargement of the metastatic nodules, combination therapy with pembrolizumab and lenvatinib (pem + len) was initiated (DAY 1). On DAY 36, her plasma glucose (PG) concentration was high; therefore, insulin degludec was administered once daily and self-monitoring of blood glucose commenced. On DAY 50, her PG and HbA1c were 509 mg/dL and 10.2%, respectively, and her insulin therapy was changed to a basal-bolus. Urinary ketones were negative. Treatment with pem + len was continued without interruption. Her GADA was negative 3 months before starting pem + len (DAY - 119), but was high (234 U/mL) on DAY 50, and then negative on DAYs 345 and 670. Her serum C-peptide concentration gradually decreased, but it did not disappear (DAYs - 119, 50, 156, 345, 607 and 670: 2.49, 1.80, 0.90, 0.21, 0.85 and 0.65 ng/mL, respectively). Human leukocyte antigen analysis revealed two susceptibility haplotypes (DRB1^*04:05-DQB1^*04:01-DPB1^*02:01 and DRB1^*04:05-DQB1^*04:01-DPB1^*05:01) for type 1 diabetes (T1D). This case is notable in that pembrolizumab-related T1D progressed more slowly than previously reported, and lenvatinib may have contributed to this delay.