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Abstract: TH-OR121

A Global Anti B-Cell Strategy with Obinutuzumab and Daratunumab in Severe Pediatric Idiopathic Nephrotic Syndrome

Session Information

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Dossier, Claire, APHP, Robert-Debre Hospital, Paris, France
  • Prim, Benjamin, APHP, Robert-Debre Hospital, Paris, France
  • Moreau, Christelle, APHP, Robert-Debre Hospital, Paris, France
  • Kwon, Theresa, APHP, Robert-Debre Hospital, Paris, France
  • Couderc, Anne, APHP, Robert-Debre Hospital, Paris, France
  • Alexandra, Cambier, APHP, Robert-Debre Hospital, Paris, France
  • Baudouin, Veronique, APHP, Robert-Debre Hospital, Paris, France
  • Maisin, Anne Francoise, APHP, Robert-Debre Hospital, Paris, France
  • Deschênes, Georges, Hospital Robert Debre/Pediatric Nephrology, Paris, France
Background

The efficacity of B-cell depletion and Immunoglobulin adsorption in the treatment of patients with Steroid Dependant Nephrotic Syndrome (SDNS) and Steroid Resistant NS supports the involvement of B cells in the physiopathology of INS. However, rituximab (RTX) targets only CD20 positive B-cells and especially not plasma cells. Furthermore, RTX mediated B-cell depletion may paradoxically induce the settlement of autoreactive long-lived plasma cells which may account for some RTX failure. In this pilot study, we investigate in patients with severe SDNS the association of Obinutuzumab (OBZ), a 2ndgeneration anti CD20 monoclonal antibody, with higher in vitro B-cell cytotoxicity than RTX, with Daratumumab (DAR), an anti CD38 monoclonal antibody with high plasma cell cytotoxicity in addition to an immunomodulatory activity.

Methods

Patients received an infusion of 1000mg/1,73m2 of obinutuzumab at day 0 and 1000mg/1,73m2 of daratumumab at day 15. All other immunosuppressive treatments were discontinued within two months, and biological monitoring was performed monthly until B cell recovery.

Results

9 patients with SDNS and resistance (n=3) or early relapse after prolonged B-cell depletion with rituximab (n=6) were included. Median ages at INS onset, first RTX and OBZ were respectively of 2.9, 7.7 and 10.9 years old. B-cell depletion was achieved in all patients. Median follow-up was 10 months (IQ 8.3-10.3), and all patients remained relapse-free. Six patients had still undetectable peripheral B-cells, while B-cell reconstitution occured at 7.9, 8.1 and 9.3 months in the 3 others. Mild infusion reactions were reported in 2/9 patient during OBZ and 3/9 during DAR infusions. Mild neutropenia (500-1000/mm3) occured in 2/9 patients. 7/9 patients received IV immunoglobulins because of hypo-IgG. Hypo-IgA was noted in 8 patients and hypo-IgM in all patients. No severe infection was reported.

Conclusion

Global anti-B cell strategy with obinutuzumab and daratumumab induces prolonged peripheral B-cell depletion and nephrotic syndrome remission in children with severe SDNS. However, it induces frequent and profound hypogammaglobulinemia and further investigation of the safety and the long-term efficacy of this strategy is needed.