Diabetic Ketoacidosis and Profound Insulin Resistance From Brentuximab Vedotin

Abstract

Hodgkin's lymphoma is commonly treated with a combination of chemotherapy drugs including doxorubicin, bleomycin, vinblastine, and dacarbazine. Antibody-drug conjugates such as brentuximab vedotin are now being used to treat Hodgkin's lymphoma that has not responded to standard treatment. Brentuximab vedotin is a monoclonal antibody that selectively delivers a cytotoxic agent, monomethyl auristatin E, which targets cells expressing surface CD30 markers, a protein that may be found in high amounts in some cancer cells including lymphoma cells. Common adverse effects of the drug include diarrhea, nausea, anemia, and fatigue. We present a case of a patient with diabetic ketoacidosis and profound insulin resistance secondary to brentuximab. Diabetic ketoacidosis is a rare but serious adverse reaction in this growing class of antibody-drug conjugates.

Refractory insulin resistance and hemophagocytic lymphohistiocytosis following enfortumab vedotin treatment: A case report

“…Ketoacidosis presentations similar to those seen with EV were also observed with another MMAE-containing drug, brentuximab vedotin, used in Hodgkin's lymphoma (18,19). Other drugs within this family, as revealed in phase I studies, were associated with a notable proportion of patients encountering grade ≥3 hyperglycemia (20,21).…”

Severe insulin resistance in a patient with diabetes after treatment with brentuximab vedotin

“…Studies reporting the occurrence of hyperglycaemia following the initiation of BV treatment are limited. To date, five patients who developed DKA after BV administration have been reported6 11–14 (one after combination BV, nivolumab and ipilimumab), and only one in a pre-diabetes state experienced persistent hyperglycaemia 15. To the best of our knowledge, this case report is the first to document the occurrence of severe hyperglycaemia due to extreme IR after BV treatment in a patient with known diabetes.…”

“…Thakkar et al presented an overweight woman in her late 40s with no history of diabetes who received insulin therapy as a treatment for DKA. Her blood glucose levels remained normal 2 weeks after hospital discharge 14…”

“…BV-induced hyperglycaemia is a rare side effect. Five patients reported the onset of diabetic ketoacidosis, and one the onset of diabetes mellitus after the initial BV infusion 6 11–15. The corresponding hyperglycaemia can be life-threatening, and early recognition of this side effect enables early treatment.…”

Severe Cytokine Release Syndrome and Hemophagocytic Lymphohistiocytosis (HLH)-Like Syndrome Following Administration of Combined Brentuximab Vedotin and Nivolumab for Recurrent Classical Hodgkin Lymphoma: A Case Report

“…to ICIs or BVs. [22][23][24] It is unclear whether BV, nivolumab, or the combination triggered the hyperinflammatory response in our patient. Moreover, we cannot exclude progression of cHL, given the new splenomegaly found on the patient's admission, as a contributor to the HLH-like presentation.…”