Rituximab for the treatment of immune checkpoint inhibitor-induced glomerulonephritis

Among patients receiving immune checkpoint inhibitor (ICI) therapy, the most common renal immune-related adverse event is interstitial nephritis, which is caused by severe T-cell infiltration and is typically responsive to steroids; although rarer, autoimmune induction in the kidney has also been reported. There is a paucity of data regarding ICI-induced autoimmune disease in the kidney and the challenges associated with continuing ICI therapy. Here, we present a single center case series of ICI-induced glomerulonephritis with data on treatment rechallenge.

We retrospectively reviewed 241 patients who underwent kidney biopsies at our institution between 2015 and 2024 and identified those who had non-vasculitis-associated glomerulonephritis after ICI therapy. Demographics, renal toxicity, renal response, disease response, and overall survival data were extracted from the patients' medical records. We defined renal response based on creatinine and proteinuria using KDIGO guidelines. We also performed a literature review to identify published cases of ICI-induced glomerulonephritis. Differences between treatment groups were assessed with a two-sided, two-sample t-test and Wilcoxon test or with a chi-square test, as appropriate.

Among 241 kidney biopsies we identified 16 patients with non-vasculitic GN, eight received rituximab with or without corticosteroids, and eight received corticosteroids only, for ICI-induced glomerulonephritis. The median proteinuria grades in the rituximab and corticosteroid groups were 3 and 1, respectively. The median corticosteroid treatment duration in the rituximab group (2.5 weeks) was shorter than that in the corticosteroid group (8 weeks). In the rituximab group, 75% of patients underwent ICI rechallenge and had no proteinuria relapse. Patients who received rituximab had better change in proteinuria response than those who received corticosteroids (P value = .029). Among the 42 patients we identified from the literature review, renal response did not differ significantly between the 10 who received rituximab and the 32 who did not.

Use of Rituximab in treatment of ICI-induced GN is an attractive option to reduce steroids exposure allowing continued ICI treatment for overall improved renal outcome. Clinical trials to evaluate these findings are needed.