Kidney Week 2025 Annual Meeting-Optimizing B Cell-Targeted Therapies for Lupus Nephritis: Strategies for Success and Pitfalls to Avoid

Video Transcription

Video Summary

Laura Ferreira Provenzano (Cleveland Clinic) introduces an ASN symposium on optimizing B‑cell–targeted therapies for lupus nephritis (LN), emphasizing LN’s frequency, severity, and persistently low complete remission rates despite standard induction therapy. She frames the central challenge: lupus is a complex autoimmune disease, and B cells contribute through autoantibody production, antigen presentation, T‑cell activation, and pro‑inflammatory cytokine secretion. She reviews the LUNAR trial, where adding rituximab to mycophenolate plus steroids did not improve complete renal response at 52 weeks, though it improved serologies, proteinuria trends, and reduced need for rescue cyclophosphamide. Observational data suggest rituximab benefits refractory LN, and post‑hoc analyses indicate outcomes may depend on depth/duration of B‑cell depletion.<br /><br />Augusto Baglio (University of Florence) compares B‑cell pathobiology across LN, ANCA‑vasculitis, and membranous nephropathy. In LN, impaired clearance of apoptotic material and dysregulated NETosis expose nuclear antigens, driving type I interferon responses and BAFF‑mediated expansion of autoreactive transitional B cells. Lupus B cells have lowered activation thresholds and reduced inhibitory FcγR2B signaling, and they can infiltrate kidneys, forming lymphoid aggregates/tertiary lymphoid structures that perpetuate disease. He argues durable control may require “immune reset” via deeper tissue B‑cell depletion (e.g., obinutuzumab, T‑cell engagers, CAR‑T), noting rituximab may incompletely clear lymphoid tissue B cells.<br /><br />Michael Choi reviews emerging therapies: phase 3 data suggest obinutuzumab plus mycophenolate/steroids increases complete renal response but with infection/neutropenia concerns (notably during early COVID). Small reports show daratumumab may help refractory LN. CD19 CAR‑T studies show dramatic activity reductions and medication‑free remissions in some patients, but pooled data show variable responses and risks (CRS, ICANS, serious infections, rare secondary T‑cell malignancies), raising unresolved questions about ideal candidates, timing, and long‑term safety. Q&A highlights limited data on interferon signature changes post–CAR‑T and skepticism about prophylactic tocilizumab.

Asset Subtitle

Moderator(s): Laura Ferreira Provenzano

Presentation(s):

Introduction - Laura Ferreira Provenzano
Review of B Cell Pathobiology in Lupus: Similarities and Differences Compared with Other Autoimmune Kidney Diseases - Augusto Vaglio
B Cell-Targeted Therapies in Lupus Nephritis - Michael Choi

Support is provided by an educational grant from Genentech, a member of the Roche Group.

Meta Tag

Date 11/7/2025

Pathway 1 Glomerular Diseases

Pathway 2 Pharmacology

Session ID 519082

Keywords

lupus nephritis

B-cell targeted therapy

rituximab

LUNAR trial

obinutuzumab

BAFF

type I interferon

tertiary lymphoid structures

daratumumab

CD19 CAR-T