Endocrine Abstracts

JOINT2301

Background: Pembrolizumab is a monoclonal antibody that inhibits PD-1 activity, enhancing cell-mediated cancer cell killing. However, it inadvertently increases the risk of autoimmunity and, in transplant patients, the incidence of graft failure.

Case presentation: A 50-year-old male presented to the hospital due to worsening hyperglycemia over 4 months. He had a past medical history of Type 1 Diabetes Mellitus, End Stage Renal Disease status post Kidney and Pancreatic transplant in 2007, reportedly compliant with Tacrolimus and Prednisone, recently diagnosed with Colon Cancer with metastasis to the transplanted kidney resulting in resection and reinitiation of hemodialysis, he is currently on Pembrolizumab which was started 4 months ago. He denied any fever, rash, polyuria, or diarrhea but reported abdominal pain. He has been off insulin since his transplant but was restarted on a basal-bolus insulin regimen 4 months ago for progressively elevated glucose levels uncontrolled by an insulin sliding scale. Vital signs were normal. Physical examination was unremarkable. Diagnostic tests showed Glucose 400 mg/dL, Beta-Hydroxybutyrate 1.8 mmol/l (ref <0.5 mmol/l), blood gas pH 7.43, HCO3 23, CO2 36, HbA1C 7%, C-peptide <0.10 ng/mL (ref 0.5-2 ng/mL), Lipase 20 IU/l, TSH and cortisol were normal. Abdominal ultrasound showed normal size and vasculature of the transplanted pancreas. The patient opted for an outpatient pancreatic biopsy. Endocrinology, Oncology, and Transplant teams were consulted, Pembrolizumab was discontinued, his basal-bolus insulin regimen was adjusted, and immunosuppressants were continued. His glucose control improved, and he was discharged with a close outpatient follow-up for further work-up.

Discussion: Our patient’s worsening hyperglycemia is likely secondary to pancreatic transplant failure with concerns for the recurrence of autoimmune diabetes from Pembrolizumab. Pembrolizumab works by enhancing the cell-mediated killing of malignant cells. However, it can inadvertently attack donor alloantigens in the transplanted kidneys causing graft failure. Although, the recurrence of autoimmune diabetes in a transplanted pancreas is rare since immunosuppressants effectively control autoimmunity, the concomitant use of Pembrolizumab can inhibit immunosuppression and cause a resurgence of autoimmunity.

Conclusion: Pembrolizumab remains central in the management of multiple malignancies. However, its use is associated with risks for autoimmune endocrinopathies and organ transplant rejection. Therefore, all physicians should properly educate patients regarding the risks and benefits of treatment and ensure close multidisciplinary follow-up.

Reference: Anupam Kotwal, Candace Haddox, Matthew Block, Yogish C Kudva - Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes: BMJ Open Diabetes Research & Care 2019;7:e000591.