Abstract:
Introduction: B-cell depletion with rituximab (RTX) induces sustained remission in children with Steroid-Dependent or Frequent Relapsing Nephrotic Syndrome (SD/FRNS). However, most patients relapse after B-cell recovery and some do not achieve B-cell depletion. We report our experience of low dose Obinutuzumab (OBI), a 2ndgeneration anti-CD20 antibody in this population.
Material & Methods: This is a retrospective study of children with FR/SDNS and resistance or relapse after rituximab, treated at Robert-Debre hospital, with a single infusion of 300mg/1,73m² of OBI, and >6 months follow-up. Oral immunosuppressors were discontinued within 2 months.
Results: 32 patients were included. Median ages at INS onset, first RTX and first OBI injection were 3.9, 8.8 and 10.7 years old, respectively. Indication for OBI were: no B-cell depletion (n=7) or short depletion <3 months (n=2), Antirituximab Antibodies (n=1) or relapse after B-cell recovery following RTX (n=22). B-cell depletion was achieved in all patients, with a longer duration compared to prior RTX. At last follow up (median 18 months), B-cell recovery had occurred in 27 patients after a median depletion of 8.3 months [IQ 6.1-12.3]. 8 patients relapsed (25%), after a median time of 16 months. Mild infusion reactions occured in 5 patients and neutropenia grade 2-3 in 7 patients. IgM were low in 7 patients at baseline, and 21 during follow-up. One patient was hospitalised for infectious pneumonia and another for Acute-Lung Injury with complete recover.
Conclusion: A single low-dose of obinutuzumab is effective in children with FR/SDNS, including those resistant to rituximab. Tolerance profile is comparable to that of Rituximab but long term monitoring of Immunoglobulin levels is mandatory as well as a face to face trial with rituximab.
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