Successful Treatment of Patients With Refractory PLA2R-Associated Membranous Nephropathy With Obinutuzumab: A Report of 3 Cases

Abstract

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Rituximab, a type I anti-CD20 antibody, has been shown to be an effective therapy in treatment of patients with MN associated with M-type phospholipase A₂ receptor (PLA₂R) antibodies. Despite its effectiveness, up to 40% of patients may fail to respond to rituximab, which may be related to higher PLA₂R antibody titers. Obinutuzumab, a type II anti-CD20 depleter, has been shown to produce a more profound CD20 depletion and be more efficacious in treating certain hematologic malignancies compared with rituximab. We report 3 patients with PLA₂R-associated MN for whom rituximab failed to induce immunologic or clinical remisison, but who were successfully treated with obinutuzumab. Obinutuzumab resulted in complete immunologic remission in all 3 cases and was followed by partial remission in 2 of the cases. Obinutuzumab appears to be a promising treatment strategy for PLA₂R-associated MN that fails to respond to rituximab.

Keywords: B cell depletion; Membranous nephropathy (MN); PLA(2)R; case report; nephrotic syndrome; obinutuzumab; rituximab.