Additive Obinutuzumab Achieves High Remission Rates in Rituximab-Refractory Membranous Nephropathy

Abstract

Introduction: Rituximab has become the first-line therapy for patients with membranous nephropathy (MN). However, approximately 30-40% of patients with MN do not respond to rituximab. We presented our single-center experience of treating rituximab-refractory MN with obinutuzumab which is a humanized and glycoengineered type II anti-CD20 monoclonal antibody.

Methods: Seventeen patients with rituximab-refractory phospholipase A2 receptor (PLA2R)-associated MN who received obinutuzumab at the First Affiliated Hospital of Xi'an Jiaotong University were included in this case series study. Clinical and laboratory parameters were evaluated at presentation, before and after obinutuzumab administration.

Results: Of all patients with an average age of 49.7 ± 13.7 years, 11 (64.7%) patients were men. The median disease duration was 12 (12, 42) months. At presentation, the proteinuria and serum albumin levels were 7.51 ± 3.55 g/day and 22.1 ± 3.6 g/L, respectively. The mean estimated glomerular filtration rate level was 103.5 ± 12.9 mL/min/1.73 m2, and the patients had a baseline anti-PLA2R level of 183.2 ± 92.9 RU/mL. At obinutuzumab administration, proteinuria and albumin levels were still consistent with nephrotic syndrome. After a median follow-up of 12.6 ± 5.0 months, complete remission was achieved in 9 (52.9%) and partial remission was achieved in 6 (41.2%) cases. Of the patients who achieved remission, the median remission time was 4.4 (4.0, 6.0) months. At 6 months, 12 (70.6%) patients achieved remission and 11 of 12 patients with available PLA2R measurements reached immunological remission.

Conclusion: Obinutuzumab may represent an attractive alternative therapy in rituximab-refractory patients. Larger prospective studies are needed to validate these findings.

Keywords: Anti-phospholipase A2 receptor antibody; Membranous nephropathy; Obinutuzumab; Rituximab-refractory.

Fig. 1.

Changes in clinical parameters within 6 months after RTX administration. a Twenty-four-hour urinary protein excretion did not decrease (blue), and serum albumin did not increase (red) after RTX administration. b Scr and eGFR remained stable compared to baseline after RTX administration. c Changes in anti-PLA₂R antibody levels at 0, 4, and 6 months after RTX administration. d Circulating CD19+ B cells at 0, 0.5, and 6 months after RTX infusion. Data represent means ± SD. eGFR, estimated glomerular filtration rate; Scr, serum creatinine; PLA₂R, phospholipase A₂ receptor.

Fig. 2.

Changes in clinical parameters within 9 months after obinutuzumab administration. a Twenty-four-hour urinary protein excretion significantly decreased (blue) and serum albumin levels significantly increased (red) after obinutuzumab administration. b Scr and eGFR remained stable compared to baseline after obinutuzumab administration. c Changes in anti-PLA₂R antibody levels at 0, 4, 6 and 9 months after obinutuzumab administration. d Circulating CD19+ B cells at 0, 4, 6 and 9 months after obinutuzumab infusion. Data represent means ± SD. eGFR, estimated glomerular filtration rate; Scr, serum creatinine; PLA₂R, phospholipase A₂ receptor.

Fig. 3.

Kaplan-Meier curves for the probability of reaching the combined end point of CR or PR of NS after obinutuzumab administration in the study group considered as a whole.