Pulmonary-renal syndrome under Dostarlimab, a recent PD-1 inhibitor, in a patient with Endometrial Cancer.

Abstract

Immune checkpoint inhibitors (ICIs) have been increasingly used in the treatment of various cancers since 2011. Dostarlimab is a recent anti-PD-1 agent, approved notably as a first-line treatment for endometrial cancer. The renal toxicity of anti-PD-1 agents is rare, with a prevalence ranging from 1 to 5% depending on the studies, mainly manifesting as acute interstitial nephritis and, much more rarely, as glomerulopathies. In this article, we report a case of pulmonary-renal syndrome occurring under dostarlimab in a 77-year-old woman treated for metastatic endometrial cancer. After three treatment cycles, she developed a nephrotic syndrome with KDIGO stage 3 acute kidney injury (AKI). Immunological testing revealed positive anti-nuclear antibodies at a titer of 1:80 and positive MPO-ANCA at 5.8 U/mL. Kidney biopsy revealed necrotizing crescentic glomerulonephritis with 75% recent lesions. Immunofluorescence revealed IgG and C3 deposits. This condition was attributed to dostarlimab, which was discontinued, and IV corticosteroid therapy was initiated. After the third bolus, the patient experienced massive intra-alveolar hemorrhage, leading to a diagnosis of pulmonary-renal syndrome. She was treated with IV cyclophosphamide (500 mg). The evolution was satisfactory on the pulmonary level but without renal improvement, leading to discussion about kidney replacement therapy. To our knowledge, this is the first reported case of pulmonary-renal syndrome associated with dostarlimab, and we found it noteworthy to report, particularly given the favorable pulmonary evolution under cyclophosphamide IV.