{
  "abstract": "Objectives 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). These exploratory analyses aimed to evaluate histological remission and kidney tissue-level B-cell depletion at W76 in patients treated with OBI+ST vs PBO+ST.Methods Paired baseline and W76 kidney biopsies from REGENCY participants with biopsy-proven proliferative LN were analysed. Histological 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 histological or near-histological 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.Results 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. Most patients in the OBI+ST group had substantial drops in kidney tissue B-cell counts 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).Abstract PT2:06 Figure 1(A) Proportion of patients achieving AI≤1 and AI=0, (B) change in AI from first to repeat post-W76 biopsy and (C) change in chronicity index from first to repeat post-W76 biopsyAbstract PT2:06 Figure 2Tissue CD79a+/CD138− B cells and plasma cells at baseline and week 76 in the REGENCY longitudinal kidney biopsy B-cell cohortConclusions In the largest longitudinal kidney biopsy cohort ever reported for a registrational LN clinical trial, significantly more patients achieved complete or near-complete histological 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 histological outcomes in future LN trials and highlight a potential mechanism for obinutuzumab in preserving long-term kidney health.",
  "authors": [
    {
      "affiliations": [
        "Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA"
      ],
      "name": "Brad H Rovin"
    },
    {
      "affiliations": [
        "F. Hoffmann-La Roche Ltd, Basel, Switzerland"
      ],
      "name": "Elsa Martins"
    },
    {
      "affiliations": [
        "Genentech, Inc., South San Francisco, CA, USA"
      ],
      "name": "Cary D Austin"
    },
    {
      "affiliations": [
        "Genentech, Inc., South San Francisco, CA, USA"
      ],
      "name": "Harini Raghu"
    },
    {
      "affiliations": [
        "Genentech, Inc., South San Francisco, CA, USA"
      ],
      "name": "Caleb Chan"
    },
    {
      "affiliations": [
        "Genentech, Inc., South San Francisco, CA, USA"
      ],
      "name": "Patrick S Chang"
    },
    {
      "affiliations": [
        "Genentech, Inc., South San Francisco, CA, USA"
      ],
      "name": "Jay P Garg"
    },
    {
      "affiliations": [
        "Pathology Unit, Fernandez Hospital, Buenos Aires, Argentina"
      ],
      "name": "Valeria Alberton"
    },
    {
      "affiliations": [
        "Bahiana School of Medicine and Public Health and UFBA, Federal University of Bahia, Salvador, Brazil"
      ],
      "name": "Mittermayer B Santiago"
    },
    {
      "affiliations": [
        "Universidad Simón Bolívar y Clínica de la Costa, Barranquilla, Colombia"
      ],
      "name": "Gustavo Aroca-Martínez"
    },
    {
      "affiliations": [
        "Centro de Investigación y Tratamiento Reumatológico S.C.,, Mexico City, Mexico"
      ],
      "name": "Fedra I Palazuelos"
    },
    {
      "affiliations": [
        "Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland"
      ],
      "name": "Teresa Baczkowska"
    },
    {
      "affiliations": [
        "Instituto Peruano del Hueso y la Articulación, Lima, Peru"
      ],
      "name": "Jose Alfaro"
    },
    {
      "affiliations": [
        "Clínica San Juan Bautista, Unidad de Investigación en Reumatología e Inmunología, Lima, Peru"
      ],
      "name": "Jorge Ravelo-Hernández"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Northwell Health, Great Neck, NY, USA"
      ],
      "name": "Richard A Furie"
    },
    {
      "affiliations": [
        "Internal Medicine and Rheumatology, Hospital Pablo Tobón Uribe, Medellín, Colombia"
      ],
      "name": "Luis F Pinto"
    },
    {
      "affiliations": [
        "Sanatorio Allende, Córdoba, Argentina"
      ],
      "name": "Eduardo H Albiero"
    },
    {
      "affiliations": [
        "Arkana Laboratories, Little Rock, AK, USA"
      ],
      "name": "Christopher Larsen"
    },
    {
      "affiliations": [
        "Genentech, Inc., South San Francisco, CA, USA"
      ],
      "name": "Bongin Yoo"
    },
    {
      "affiliations": [
        "Roche Products Ltd, Welwyn Garden City, UK"
      ],
      "name": "Jennifer Pulley"
    },
    {
      "affiliations": [
        "Genentech, Inc., South San Francisco, CA, USA"
      ],
      "name": "Andrew Thorley"
    },
    {
      "affiliations": [
        "F. Hoffmann-La Roche Ltd, Basel, Switzerland"
      ],
      "name": "Thomas Schindler"
    },
    {
      "affiliations": [
        "Genentech, Inc., South San Francisco, CA, USA"
      ],
      "name": "Theodore A Omachi"
    },
    {
      "affiliations": [
        "Genentech, Inc., South San Francisco, CA, USA"
      ],
      "name": "William F Pendergraft"
    },
    {
      "affiliations": [
        "Organización Médica de Investigación, Buenos Aires, Argentina"
      ],
      "name": "Ana Malvar"
    }
  ],
  "title": "PT2:06 Obinutuzumab induces histological remission and deep kidney parenchymal B-cell depletion in patients with lupus nephritis: exploratory analyses of the phase III regency trial",
  "uid": "f738df9d-4899-5098-85b0-c24a1b3fb1aa"
}