New Haven, CT—Cancer treatment has been transformed by the use of monoclonal antibodies (mAbs) that block immune inhibitory ligands CTLA-4 and PD-1, known as immune checkpoint inhibitors (CPIs).

With these options for treatment of cancers that are resistant to conventional cancer therapies, the life expectancy of patients with melanoma, lung cancer, renal cell carcinoma, and other cancers, has shown significant improvement.

A new review in the journal Diabetes points out that the powerful cancer drugs are not without downsides, however.

Yale University–led study authors point out that insulin-dependent diabetes can occur in CPI-treated patients. The team reviewed cases over a 6-year period at two academic institutions to identify 27 patients in whom the adverse effect had occurred, for an incidence of 0.9%.

The patients, all of whom had malignant solid-organ cancers, had received either anti–PD-1 or anti–PD-L1 antibodies. Among the group, the researchers noted that diabetes presented with ketoacidosis in 59%, while 42% had evidence of pancreatitis in the peridiagnosis period. At least one positive autoantibody was identified in 40% of the patients, with 21% having two or more.

The reviewers point out that HLA-DR4, a biomarker for autoimmune diseases, was present in 76% of patients. Immune adverse events were documented in 70% and endocrine adverse events in 44%, they add.

“We conclude that autoimmune, insulin-dependent diabetes occurs in close to 1% of patients treated with anti–PD-1 or –PD-L1 CPIs,” the study authors write. “This syndrome has similarities and differences compared with classic type 1 diabetes. The dominance of HLA-DR4 suggests an opportunity to identify those at highest risk of these complications and to discover insights into the mechanisms of this adverse event.”

As use of the cancer drugs continues to increase, the researchers urge close monitoring of patients for CPI-induced diabetes. “Glucose levels and, in patients with known type 2 diabetes, A1C levels should be followed carefully in cancer patients treated with CPIs and appropriate referrals instituted as suggested. The providers should be alarmed and check baseline glucose prior to the initiation of treatment in all patients, as suggested in the consensus recommendations for management of CPI-induced diabetes by the Society for Immunotherapy of Cancer Toxicity Management Working Group.”
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