A Case of Severe Diabetic Ketoacidosis Associated with Pembrolizumab Therapy in a Patient with Metastatic Melanoma

Abstract

Pembrolizumab, a monoclonal antibody against programmed cell death-1 receptor, was licensed for advanced cancers. Although the use of pembrolizumab can enhance the effect of cancer treatment, it can increase immune-related adverse events. We describe an elderly woman who developed ketoacidosis after receiving pembrolizumab to treat metastatic melanoma. In the presentation, laboratory analysis showed that hyperglycemia and anion gap metabolic acidosis was consistent with diabetic ketoacidosis. Except for pembrolizumab, no other predisposing factors were found. The blood glucose levels before using pembrolizumab were normal. The patient responded well to intravenous fluids, insulin therapy, and treatment to correct electrolyte disturbances. She was diagnosed with severe diabetic ketoacidosis (DKA) because of new-onset diabetes mellitus which associated with pembrolizumab therapy. Two months after she was discharged from the hospital, she continued to take insulin as well as metformin to treat her diabetes. Clinicians need to be alert about diabetes mellitus and ketoacidosis for patients undergoing pembrolizumab treatment.

Continuous Ketone Monitoring Consensus Report 2021

“…In healthy people plasma ketone concentrations usually range from 0-0.3 mM, but can increase to around 1 mM with prolonged exercise or fasting for 24 hours, and can increase to as high as 5-10 mM with prolonged fasting for 3 days or more. [8][9][10] In PwD, plasma ketone concentrations of 0.6 mM or greater signify an increased risk of ketoacidosis, as presented in Table 1. 11 Management of diabetes benefits from the measurement of ketones, especially for prevention of DKA.…”

“…The monoclonal antibody pembrolizumab, used for advanced cancer, binds to the programmed cell death 1 (PD-1) receptors on T-cells and activates the immune system to attack tumor cells, but in a handful of cases this drug has been reported to precipitate DKA. 9 Possible additional triggers also include omitting insulin (intentionally or in error), eating disorders, emotional stress, infections, surgery, and drugs such as corticosteroids, alcohol, and cocaine.…”

“…The panelists were from universities, hospitals, freestanding research institutes, government, and private practice. Panelists reviewed the medical literature pertaining to ten sessions, each focused on a topic related to the use of ketone monitoring: (1) physiology of ketone production, (2) measurement of ketones, (3) performance of the first CKM reported to be used in human trials, (4) demographics and epidemiology of DKA, (5) atypical hyperketonemia, (6) prevention of DKA, (7) non-DKA states of fasting ketonemia and ketonuria, (8) potential integration of CKMs with pumps and automated insulin delivery (AID) systems to prevent DKA, (9) clinical trials of CKMs, and (10) the future of CKMs. Each of the ten sessions was co-chaired by two experts (presented in alphabetical order) and all panelists participated in every session.…”

Immune-Mediated Diabetes Mellitus, Diabetic Ketoacidosis, Enteritis, and Thrombotic Thrombocytopenic Purpura Presenting as Adverse Effects of Pembrolizumab Therapy

“…The programmed cell death 1 (PD-1) receptor is an inhibitory modulator on T cells that interacts with the PD-1 ligand on self-cells. 1,2 This checkpoint prevents excessive autoimmune destruction of self-cells. Pembrolizumab is a PD-1 inhibitory monoclonal antibody used to circumvent the immune checkpoint, thus allowing for heightened T-cell activity and destruction of tumor cells.…”