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O35 B-cell depletion and response in a randomized, controlled trial of obinutuzumab for proliferative lupus nephritis
  1. Richard Furie1,
  2. Matthew D Cascino2,
  3. Jay P Garg2,
  4. Gustavo Aroca3,
  5. Analía Alvarez4,
  6. Hilda Fragoso-Loyo5,
  7. Elizabeth Zuta Santillán6,
  8. Ana Malvar7,
  9. Paul G Brunetta2,
  10. Thomas Schindler8,
  11. Cary Michael Donna Looney2,
  12. Imran Hassan9 and
  13. Brad H Rovin10
  1. 1Northwell Health Great Neck, New York
  2. 2Genentech, Inc., South San Francisco, USA
  3. 3Simon Bolivar University y Clinica de la Costa, Barranquilla, Colombia
  4. 4CEMIC, Buenos Aires, Argentina
  5. 5Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
  6. 6Instituto de Ginecología y Reproducción, Lima, Peru
  7. 7Organización Maedica de Investigación, Buenos Aries, Argentina
  8. 8F. Hoffmann-La Roche AG, Basel, Switzerland
  9. 9Hoffmann-La Roche Ltd, Mississauga, Canada
  10. 10Ohio State University, Columbus, USA

Abstract

Background Previous analyses identified associations between the degree of B-cell depletion and response in lupus nephritis (LN). NOBILITY tested whether enhanced B-cell depletion with the type II anti-CD20 mAb obinutuzumab could improve responses in LN.

Methods 126 patients with active Class III/IV LN were randomized to obinutuzumab or placebo infusions in combination with mycophenolate and corticosteroids. Peripheral B-cells were measured using a flow cytometry method with a lower limit of 0.441 cells/μL. Sustained depletion was assessed by flow cytometry measurements at weeks 24 and 52.

Results Obinutuzumab was associated with increased CRR (40% vs. 18%, P=0.007) and ORR (51% vs. 29%, P =0.015) at week 76. Obinutuzumab resulted in rapid and complete depletion of peripheral B-cells, memory and naïve B-cell subsets, and plasmablasts, with 89% of obinutuzumab patients depleted to <0.441 CD19+ cells/μL at week 4. Among obinutuzumab patients, sustained B-cell depletion was associated with greater renal response at week 76 (table 1), although patients who achieved sustained depletion also had lower baseline proteinuria and serum creatinine.

Abstract O35 Table 1

Renal responses at week 76 by depletion status

Conclusions Obinutuzumab, a type II anti-CD20 mAb, induced rapid and complete depletion of peripheral B-cells and B-cell subsets. Similar to previous reports, sustained B-cell depletion was associated with increased renal response. Further evaluation is ongoing to understand the factors associated with achievement of sustained B-cell depletion and renal response.

Acknowledgements This study was funded by F. Hoffmann-La Roche.

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