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

Klomjit, Nattawat; Fervenza, Fernando C.; Zand, Ladan

doi:10.1053/j.ajkd.2020.02.444

Cited by 67 publications

(35 citation statements)

References 21 publications

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“…The Membranous Nephropathy Trial of Rituximab (MENTOR trial) confirmed substantial uncontrolled data showing that B-cell depletion with rituximab is a However, there is an unmet need for additional treatment strategies in patients who do not tolerate these therapies, do not achieve immunologic remission with these therapies, and/or develop anti-rituximab antibodies. Case reports have shown that the "next-generation" anti-CD20 antibodies obinutuzumab [6] and ofatumumab [7][8][9] may be promising agents in such cases. Successful treatment of rituximab-resistant patients with obinutuzumab and ofatumumab could imply that additional or more complete B-cell depletion is required in such cases to achieve immunologic remission, but also that the producing anti-PLA2R antibody-producing cell is a CD20positive B cell.…”

Section: Discussionmentioning

confidence: 99%

Bortezomib Treatment for Refractory PLA2R-Positive Membranous Nephropathy

2021

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Introduction: B-cell depletion has been shown to be an effective strategy for the majority of patients with membranous nephropathy (MN), and in PLA2R-positive MN, immunologic remission (improvement or elimination of measurable serum anti-PLA2R antibodies) precedes renal remission. Yet, cases exist of patients who do not achieve immunologic remission despite achieving peripheral B-cell depletion. This has led to the hypothesis that some patients have plasma cells that are responsible for producing anti-PLA2R antibodies. Case Presentation: A 66-year-old man with a past medical history of hypertension, hyperlipidemia, and cerebrovascular disease presented with nephrotic syndrome and was diagnosed with PLA2R-positive MN on kidney biopsy. He was refractory to multiple therapies including tacrolimus, and was resistant to rituximab despite having achieved B-cell depletion. He also did not enter into remission with plasmapharesis and cyclophosphamide. He then achieved immediate immunologic remission after treatment with the proteasome inhibitor bortezomib, which is used as first-line therapy for multiple myeloma. Discussion/Conclusion: This case suggests that considering the source of PLA2R antibody production could lead to individualized and targeted therapies for MN.

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Section: Discussionmentioning

confidence: 99%

Bortezomib Treatment for Refractory PLA2R-Positive Membranous Nephropathy

2021

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“…In a recent case series of 3 patients with rituximab-refractory PLA2R MN, obinutuzumab led to complete immunologic remission and improvement in proteinuria in 2 patients. 7 In our study, obinutuzumab led to complete or partial remission in 85.7% of rituximab-refractory patients.…”

Section: Discussionmentioning

confidence: 46%

“…The idiopathic form of this disease is due to a circulating factor(s) that disrupt the glomerular filtration barrier, resulting in widespread podocyte foot process effacement (FPE) and proteinuria. [5][6][7] Reported recurrence rates following the first kidney transplantation…”

Section: Disclosurementioning

confidence: 99%

Obinutuzumab is Effective for the Treatment of Refractory Membranous Nephropathy

Sethi

Kumar

Lim

et al. 2020

Kidney International Reports

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“…3 resistant patients were treated ofatumumab, a fully J o u r n a l P r e -p r o o f humanized anti-CD20 antibody, and all achieved remission. Alternative B cell depleting agents such as ofatumumab or type II anti-CD20 Ab obinutuzumab may prove to be a safe and effective rescue therapy for patients either refractory or sensitized against rituximab, but available evidence is limited to single case reports/series 75,76 . A recently published prospective, open-label trial investigated belimumab, a monoclonal Ab inhibiting B cell production/stimulation, in a cohort of 14 patients 77 .…”

Section: Beyond Rituximab -Options For Refractory Patientsmentioning

confidence: 99%

Rituximab in Membranous Nephropathy

Gauckler

Smıth

Alberici

et al. 2021

Kidney International Reports

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

Cited by 67 publications

References 21 publications

Bortezomib Treatment for Refractory PLA2R-Positive Membranous Nephropathy

Bortezomib Treatment for Refractory PLA2R-Positive Membranous Nephropathy

Obinutuzumab is Effective for the Treatment of Refractory Membranous Nephropathy

Rituximab in Membranous Nephropathy

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