OBINUTUZUMAB INDUCES HISTOLOGIC REMISSION AND DEEP KIDNEY PARENCHYMAL B-CELL DEPLETION IN PATIENTS WITH LUPUS NEPHRITIS: EXPLORATORY ANALYSES FROM THE REGENCY TRIAL

 

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OBINUTUZUMAB INDUCES HISTOLOGIC REMISSION AND DEEP KIDNEY PARENCHYMAL B-CELL DEPLETION IN PATIENTS WITH LUPUS NEPHRITIS: EXPLORATORY ANALYSES FROM THE REGENCY TRIAL

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Brad H.
Rovin
Brad H. Rovin rovin.1@osu.edu The Ohio State University College of Medicine Department of Internal Medicine Colombus, OH United States *
Elsa Martins elsa.martins@roche.com F. Hoffmann-La Roche Ltd Division of Pharmaceuticals Basel Switzerland -
Cary D. Austin austin.cary@gene.com Genentech, Inc. Division of Pharmaceuticals South San Francisco, CA United States -
Harini Raghu raghu.harini@gene.com Genentech, Inc. Division of Pharmaceuticals South San Francisco, CA United States -
Caleb Chan chan.caleb@gene.com Genentech, Inc. Division of Pharmaceuticals South San Francisco, CA United States -
Patrick S. Chang changp9@gene.com Genentech, Inc. Division of Pharmaceuticals South San Francisco, CA United States -
Valeria Alberton vgalberton@yahoo.com.ar Fernández Hospital Pathology Unit Buenos Aires Argentina -
Mittermayer B. Santiago mitter.santiago@serdabahia.com.br Federal University of Bahia, and Clínica SER da Bahia Bahiana School of Medicine and Public Health and UFBA Salvador Brazil -
Gustavo Aroca-Martínez garoca1@clinicadelacosta.co Universidad Simón Bolívar Clínica de la Costa Barranquilla Colombia -
Jose Alfaro jlalfarolozano@gmail.com Instituto Peruano del Hueso y la Articulación Reumatología Lima Peru -
Richard A. Furie RFurie@northwell.edu Northwell Health Division of Rheumatology Great Neck, NY United States -
Christopher Larson chris.larsen@arkanalabs.com Arkana Laboratories Nephrology Little Rock, AK United States -
Bongin Yoo yoo.bongin@gene.com Genentech, Inc. Division of Pharmaceuticals South San Francisco, CA United States -
William F. Pendergraft pendergraft.will@gene.com Genentech, Inc. Division of Pharmaceuticals South San Francisco, CA United States -
Ana Malvar avmperrin@yahoo.com.ar Organización Médica de Investigación Reumatología Buenos Aires Argentina -

The REGENCY trial (NCT04221477) demonstrated superiority of obinutuzumab (OBI) plus standard therapy (+ST) vs placebo (PBO) +ST in achieving complete renal response (CRR) at Week 76 (W76) in adults with active lupus nephritis (LN). It was postulated that OBI+ST would yield greater rates of histologic remission and kidney tissue-level B-cell depletion at W76 than PBO+ST, which would portend more favorable long-term kidney outcomes, such as reduced LN flare risk and preserved kidney function. These exploratory analyses aimed to evaluate histologic remission and kidney tissue-level B-cell depletion at W76 in patients treated with OBI+ST vs PBO+ST.

Paired baseline and W76 kidney biopsies from REGENCY participants with biopsy-proven proliferative LN were analyzed. Histologic analysis: 64 biopsies (32 OBI+ST, 32 PBO+ST) were evaluated using the 2018 ISN/RPS LN classification, along with the NIH activity (AI) and chronicity indices. The proportion of patients achieving histologic or near-histologic remission (AI=0 or ≤1) was determined. B-cell analysis: 29 participants (14 OBI+ST, 15 PBO+ST) were assessed. CD79a+/CD138− B cells were quantified by immunofluorescence microscopy and digital whole-slide analysis. Changes in B-cell counts at W76 were compared using an ANCOVA model, adjusting for baseline B-cell counts and stratification factors.

Baseline characteristics were balanced, despite higher tissue B-cell levels in the OBI+ST group. At W76, significantly more patients achieved AI=0 or ≤1 with OBI+ST vs PBO+ST (Figure 1). Among patients not achieving CRR, 52.6% (10/19) in the OBI+ST group had an AI=0 at W76, vs 8.3% (2/24) in the PBO+ST group. Nearly every patient in the OBI+ST group had their kidney tissue B-cell count drop substantially, approaching zero, by W76 (Figure 2). The adjusted mean change in B-cell counts from baseline to W76 was −28.5 (95% CI, −33.3 to −23.6) for OBI+ST vs −11.9 (95% CI, −16.6 to −7.2) for PBO+ST, a significant difference of −16.6 (95% CI, −23.4 to −9.7; P<0.0001).

Figure 1

In the largest longitudinal kidney biopsy cohort ever reported for a registrational LN clinical trial, significantly more patients achieved complete or near-complete histologic remission with OBI+ST vs PBO+ST. This is the first demonstration of deep kidney tissue B-cell depletion by any anti-CD20 agent, in any glomerular disease. Obinutuzumab’s potent B-cell clearance from kidney tissue may drive kidney function improvement and LN flare reduction. These findings support assessment of histologic outcomes in future LN trials and highlight a potential mechanism for obinutuzumab in preserving long-term kidney health. This abstract was also submitted to the ACR and ASN 2025 congresses.

Kewords