B264 - Obinutuzumab and Daratumumab to the Rescue: Primary Focal Segmental Glomerulosclerosis (FSGS) Diagnosed After Kidney Transplant

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Author Block: C. T. Faldu, A. Gogoli, S. Virmani, Y. Radhakrishnan, University of Virginia, Charlottesville, VA
*Purpose: Primary FSGS (pFSGS) poses a significant risk of allograft loss post kidney transplantation. New onset and rapid progression of proteinuria often leads to the diagnosis along with confirmation with an allograft biopsy. Treatment-resistant pFSGS may require B-cell depletion therapy to prevent recurrence, such as obinituzumab. Combination therapy with anti-CD38 (daratumumab) has been showcased in case reports to be effective in achieving complete remission. We present a newly diagnosed pFSGS post-transplant with complete remission (0.8 g/d proteinuria) after treatment with obinutuzumab (1 dose) and daratumumab (2 doses).
*Methods: A 65-year-old female with ESRD from presumed hypertensive nephrosclerosis, presented with acute kidney injury and new onset proteinuria (> 3 g/d ) 24 weeks post kidney transplant. Biopsy revealed widespread foot process effacement (Image 1) along with Acute T-Cell Rejection (TCMR). She was treated with pulse dose steroids, IVIG, thymoglobulin 4.5mg/kg, plasma exchange (PLEX), mycophenolate 1g twice daily and tacrolimus with a goal of 8-10 mg/d. Proteinuria improved to 0.8g/d but increased 4 weeks later with peak levels of 16 g/d. PLEX was repeated along with pulse steroids. Due to rapid recurrence of proteinuria, obinutuzumab (1 dose) and daratumumab (planned for 8 doses) were added to the treatment plan.
*Results: She received 2 doses of daratumumab after a shared decision with the patient due to difficulty receiving outpatient treatment. Proteinuria improved to 0.8 g/d 4 weeks after PLEX plus combined obinutuzumab and daratumumab (see Image 2). See trend proteinuria the trend in Figure 1. 3 months post-treatment, creatinine returned to nadir post-transplant at 2.0 mg/dL. .
*Conclusions: Combined use of obinutuzumab and daratumumab, even with a few doses, shows promising results in recurrence of pFSGS post-transplantation. Further research is needed on proper dosing and timing of therapies to avoid allograft loss.