PD-1 Inhibitor Immune-Related Adverse Events in Patients With Preexisting Endocrine Autoimmunity

Immune checkpoint inhibitors, including monoclonal antibodies directed against programmed cell death protein 1 (PD-1) and its ligand, have emerged as beneficial cancer immunotherapies. These therapies are known to cause immune-related side effects; however, their role in patients with a preexisting autoimmune disease is not clear.

We describe two cases of anti-PD-1 immune-related adverse events. A 52-year-old male with longstanding type 1 diabetes (T1D), long-term stable kidney transplant, and hypothyroidism received two separate anti-PD-1 monoclonal antibodies for metastatic melanoma. The patient developed acute kidney graft rejection requiring hemodialysis and worsening of autoimmune hypothyroidism 3 weeks after starting treatment. He continued anti-PD-1 treatments and remained on hemodialysis and increased levothyroxine dosage. The second case is a 62-year-old male with no previous history of diabetes who received anti-PD-1 treatment and developed severe diabetic ketoacidosis (DKA) 5 days following the start of therapy. Further laboratory testing revealed high titer antibodies directed against glutamic acid decarboxylase. These antibodies, which were of the IgG isotype and involved in memory immune responses, were likely present before anti-PD-1 treatment. He also had human leukocyte antigen genes that confer T1D genetic risk. Despite normal pretreatment blood glucose levels and HbA1c, the patient requires permanent exogenous insulin treatment.

Patients with preexisting endocrine autoimmunity may have more frequent and severe immune-related side effects with anti-PD-1 treatment. Given the morbidity and mortality associated with solid organ transplant rejection and DKA, clinicians caring for patients receiving these state-of-the-art therapies need to be aware of the potential adverse events.