Case of fulminant type 1 diabetes induced by the anti‐programmed death‐ligand 1 antibody, avelumab

Abstract

With the expansive use of immune checkpoint inhibitors, the frequency of immune‐related adverse events, including autoimmune type 1 diabetes, has been exponentially increased. The anti‐programmed death‐ligand 1 antibody, avelumab, has recently been approved for metastatic Merkel cell carcinoma therapy. Here, we report a patient that developed fulminant type 1 diabetes during avelumab treatment. An 81‐year‐old woman with no history of diabetes received avelumab for metastatic Merkel cell carcinoma. Elevated plasma glucose level (483 mg/dL), hemoglobin A1c level (7.5%) and ketosis were observed after 10 courses of avelumab without any symptoms related to hyperglycemia. As the laboratory tests showed insulin depletion, we diagnosed her with fulminant type 1 diabetes induced by avelumab. This is the first reported case of avelumab‐induced type 1 diabetes, illustrating the necessity for close monitoring of glycemic control during avelumab therapy, as well as other immune checkpoint inhibitors.

A rapidly expanding cutaneous tumour in the context of a Janus kinase inhibitor agent following allogeneic stem cell transplant

“…A rare and important adverse effect noted in this case was onset of T1DM secondary to avelumab, which has also been reported in the literature 8 . Autoreactive T cells cause destruction of the pancreatic β cells and leads to diabetic ketoacidosis, 8 resulting in T1DM, as in our patient.…”

“…As immune evasion strategy of MCC is known to involve upregulation and recruitment of regulatory T cells, 6 we speculate that this mechanism may have contributed to the reduction in GvHD severity 7 . A rare and important adverse effect noted in this case was onset of T1DM secondary to avelumab, which has also been reported in the literature 8 . Autoreactive T cells cause destruction of the pancreatic β cells and leads to diabetic ketoacidosis, 8 resulting in T1DM, as in our patient.…”

Anti PD-1 monoclonal antibody induced autoimmune diabetes mellitus: a case report and brief review

“…And with gradually extensive use of nivolumab and pembrolizumab, several autoimmune diabetes mellitus induced by these two agents have been reported in clinical practice (13)(14)(15)(16)(17). Anti-PD-L1 agent, avelumab, also could induce rapid type 1 diabetes mellitus (18). We had summarized these reports in the Table 3.…”

Two types of fulminant type 1 diabetes mellitus: Immune checkpoint inhibitor‐related and conventional

“…The second patient developed fulminant type 1 diabetes during ICI treatment, but his endogenous insulin secretory capacity slightly improved with the discontinuation of ICI 6 . The third patient developed fulminant type 1 diabetes during the administration of ICI of programmed cell death 1 ligand 1 antibody, but not programmed cell death 1 (PD‐1) antibody 7 . The fourth patient showed a particularly rapid decrease in insulin secretory capacity during the development of fulminant type 1 diabetes 8 .…”

“…As fulminant type 1 diabetes develops in programmed cell death 1 ligand 1 antibody administration, as well as in PD‐1 antibody 8 , it seems important to block this pathway, but not each molecule. Interestingly, β‐cell damage ensues after the initial dose of ICI, but often after repeated doses of ICI in ICI‐related fulminant type 1 diabetes 4‐8 . This suggests that β‐cell destruction could be triggered only when an additional element overlaps with ICI administration.…”