The role of Obinutuzumab in rituximab-refractory membranous nephropathy and minimal change disease

ABSTRACT Background Obinutuzumab, a new-generation anti-CD20 monoclonal antibody, was originally developed to overcome resistance to rituximab in B-cell malignancies. There is limited research regarding the use of obinutuzumab in patients with rituximab-refractory membranous nephropathy (MN) and minimal change disease (MCD). Methods A retrospective analysis was performed at Changzheng Hospital from September 2022 to September 2024, and screened patients with rituximab-refractory MN or MCD. Participants were treated because they were refractory to rituximab and consented to receive infusions of obinutuzumab. Primary outcomes were defined as complete remission (CR, proteinuria <0.3 g/d) or partial remission (PR, proteinuria <3.5 g/d with a ≥50% reduction). Secondary outcome was immunological remission in patients with phospholipase A2 receptor (PLA2R)-related MN. Results Seven patients with MN and five with MCD were included in the cohort. Among patients with MN, six of seven (86%) achieved at least PR, of whom two patients reached CR with a median time to first remission (either PR or CR) of 8.0 months. Among patients with positive serum anti-PLA2R antibodies at baseline, all achieved an immunological response. No patients experienced a relapse during the follow-up period. Among patients with MCD, all patients achieved a CR with the median time of 1.0 months. Patients who were steroid-dependent or immunosuppressant-dependent were able to taper their medications in the short term without experiencing relapse. No treatment-related severe adverse events were reported. Conclusions Our study demonstrated that obinutuzumab represents a promising alternative therapeutic option for the management of rituximab-refractory MN and MCD.