Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases

Abstract

Background Membranous Nephropathy (MN) is a common cause of nephrotic syndrome (NS) in adults. Recognition of MN as an antibody mediated autoimmune disease has enabled the introduction of anti-B-cell therapy. Rituximab, a type I anti-CD20 antibody has been used in the management of MN, but has a 35-45% failure rate. Obinutuzumab, a fully humanised type II anti-CD20 monoclonal antibody produces greater CD20 depletion and is superior to rituximab in the treatment of certain B-cell malignancies. In the two reports published to date involving nine patients with M-type phospholipase A2 receptor (PLA2R) associated MN (six of whom were rituximab resistant), treatment with obinutuzumab lead to immunological remission (IR) in 75% of patients, with improvement of proteinuria, normalisation of serum albumin and stable renal function in all patients. Case presentation We report on two cases of PLA2R-associated MN, two males aged 33 and 36-years, who presented with NS and bilateral sub massive pulmonary emboli requiring anticoagulation. Both were diagnosed serologically as PLA2R-associated MN where a renal biopsy was initially deferred due to bleeding risk on anticoagulation, but later confirmed. Both patients were refractory to multiple lines of therapy including rituximab, but achieved IR, normalistation of serum albumin, improved proteinuria and stable renal function with obinutuzumab. Conclusions Our cases add to the current limited literature on the successful use of obinutuzumab in PLA2R associated MN refractory to standard therapy including rituximab.

Obinutuzumab in Refractory Membranous Nephropathy: A Case Series

“…In other sporadic case reports, obinutuzumab had demonstrated promising efficacy in complex, refractory MN, including rituximab-resistant MN, IgG4-associated MN, and MN cases with severe chronic kidney disease. 9 , 10 , 11 , 12 Our findings aligned with previous studies on rituximab-resistant patients, indicating that all 11 patients achieved remission, with 4 of them attaining CR by the end of the follow-up.…”

Case report: One case of refractory membranous nephropathy with hypokalemia after rituximab infusion was switched to obinutuzumab without recurrence of hypokalemia

“…Compared to rituximab, obinutuzumab is a more potent inducer of antibody-dependent cell-mediated cytotoxicity (ADCC) and direct cell death (DCD). Obinutuzumab is believed to lead to a deeper and more enduring depletion of the body's B-cell population and has shown effectiveness in cases where rituximab has failed (Klomjit et al, 2020;Hudson et al, 2022). However, there is ongoing debate regarding the adverse effects or toxicity of obinutuzumab compared to rituximab.…”

Diagnosis and Treatment of Membranous Nephropathy in Integrative Medicine

“…Moreover, for patients with MN resistant to RTX, ofatumumab achieves a partial or complete remission rate of up to 85.7%. [55,56] PRECAUTIONS DURING THE TREATMENT OF MN…”