Pembrolizumab-induced acquired lipodystrophy: a case report and review of the literature.

Acquired generalized lipodystrophy (AGL) is a rare complication of immune checkpoint inhibitors (ICIs) and is associated with immune-mediated loss of adipose tissue, peripheral resistance to insulin, and serious metabolic complications. Here we report a new case of ICI-induced AGL and provide an updated literature review of published cases. We report a 39-year-old female patient treated with adjuvant pembrolizumab for stage IIIC nevoid melanoma with ICI-induced AGL. After six cycles of pembrolizumab, she developed a 40 lb weight loss with fat wasting, a decreased leptin level, significant liver function abnormalities, hepatic steatosis, hypertriglyceridemia, and subsequently was found to have severe insulin dependence and resistance. No corticosteroids were given and pembrolizumab was discontinued. AGL persists at 3-year follow up and patient remains free of melanoma progression. Literature review identified an additional seven patients who developed ICI-induced acquired lipodystrophy, predominantly female. Of the identified cases, three patients received steroids without resolution of their acquired lipodystrophy, while one patient had resolution without steroid treatment. Five patients and our case were treated with ICIs for melanoma, and all had at least a partial response to treatment. ICI-induced acquired lipodystrophy is an exceedingly rare event with profound clinical consequences. Our case report and literature review better characterized the clinical course and treatment outcomes of these patients. With the increasing utilization of ICIs in treating cancer, further studies to better understand the underlying mechanism and to guide clinical management of the metabolic complications are needed.