Obinutuzumab induced remission in FSGS patient after rituximab failure in case report

IntroductionPodocytopathies such as minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remain therapeutic challenges in adults. Although corticosteroids and rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, are effective in most patients, up to 10% show resistance or relapse despite B-cell depletion. Obinutuzumab (OBZ), a humanized type II anti-CD20 monoclonal antibody, achieves deeper and more sustained B-cell depletion and may overcome RTX inadequate response.Case reportA 33-year-old woman presented with nephrotic syndrome (proteinuria 7.1 g/24 h, serum albumin 2.6 g/dL, preserved renal function). Kidney biopsy revealed primary FSGS. She achieved only partial remission with corticosteroids and cyclosporine. RTX (1 g × 2 doses) induced transient peripheral B-cell depletion but no complete remission. A second biopsy excluded chronic changes, and genetic testing for hereditary podocytopathy was negative. Thus 67 weeks after diagnosis and initial treatment with persistent proteinuria > 1g/24 h and hypoalbuminemia, the patient received OBZ (1 g × 2 doses, two weeks apart). Two months later, she achieved complete remission (proteinuria 0.2 g/24 h, serum albumin 3.7 g/dL), with sustained B-cell depletion and no adverse events. A repeat administration of OBZ (1 g) was performed 10 months later due to B-cell repopulation, rising proteinuria (0.6 g/24 h), and mild hypoalbuminemia (serum albumin 3.4 g/dL), successfully re-inducing complete remission (proteinuria 0.2 g/24 h, serum albumin 3.8 g/dL).DiscussionThis case illustrates the potential of OBZ as an effective therapeutic option in podocytopathies with RTX inadequate response. The superior efficacy of OBZ may result from enhanced antibody-dependent cellular cytotoxicity, depletion of tissue-resident B cells, and reduced immunogenicity compared with RTX. OBZ may thus offer an alternative in refractory MCD/FSGS.