Rescue with obinutuzumab and daratumumab as combined B cell/plasma cell targeting approach in severe posttransplant focal segmental glomerulosclerosis recurrence

Am J Transplant. 2024 Oct;24(10):1896-1900. doi: 10.1016/j.ajt.2024.06.010. Epub 2024 Jul 17.

Abstract

The recurrence of primary focal segmental glomerulosclerosis (FSGS) after kidney transplantation is associated with a high graft loss rate with standard treatments based on plasmapheresis with/without rituximab. We present 2 consecutive cases of nongenetic early severe recurrent FSGS refractory to rituximab and anti-interleukin 1 treatment and with a partial response to plasmapheresis. Case 1 was a 22-year-old man who was rescue-treated for recurrence 36 weeks after transplantation with obinutuzumab (1000 mg/1.73 m2, 1 dose) and daratumumab (18 mg/kg each dose, 8 doses), resulting in plasmapheresis discontinuation and a drop of proteinuria from 29 to 2.3 g/d. Proteinuria increased with circulating CD38+ plasma cells and responded to an additional daratumumab dose. Currently, the proteinuria is 1.8 g/d, 14.5 months after discontinuing plasmapheresis and starting obinutuzumab and daratumumab therapy. Case 2 was a 15-year-old girl who was plasmapheresis dependent with 2 g/d proteinuria 82 weeks after transplantation, with a Tesio catheter in the right jugular vein as the only possible vascular access. After treatment with obinutuzumab and daratumumab (1 dose each), she achieved stable complete remission (0.3 g/d proteinuria) with persistent plasmapheresis discontinuation. These cases suggest the potential of combining obinutuzumab with daratumumab for the treatment of recurrent FSGS.

Keywords: daratumumab; focal segmental; kidney transplant; obinutuzumab.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal* / therapeutic use
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • B-Lymphocytes / drug effects
  • Female
  • Glomerular Filtration Rate
  • Glomerulosclerosis, Focal Segmental* / drug therapy
  • Glomerulosclerosis, Focal Segmental* / etiology
  • Graft Rejection / drug therapy
  • Graft Rejection / etiology
  • Graft Survival / drug effects
  • Humans
  • Kidney Transplantation* / adverse effects
  • Male
  • Plasma Cells / pathology
  • Plasmapheresis
  • Postoperative Complications / drug therapy
  • Prognosis
  • Recurrence*
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal
  • daratumumab
  • obinutuzumab