Pediatric nephrology (Berlin, Germany) · 2025
Obinutuzumab as a therapeutic option for SDNS children resistant to rituximab with anti-RTX antibodies.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Parmentier Cyrielle, Mary Anne-Lise, Diep Antoine, Hogan Julien, Ulinski Tim, Mignot Sabine, Dossier Claire
Аннотация
BACKGROUND: B-cell-depleting agents like rituximab (RTX) are central to treating severe steroid-dependent idiopathic nephrotic syndrome (SDNS) and frequent relapses. However, RTX can induce anti-RTX antibodies (ARA) that compromise efficacy. Obinutuzumab, a fully humanized anti-CD20 antibody, may overcome RTX resistance. We evaluate obinutuzumab's safety and efficacy in pediatric SDNS patients who developed ARA after RTX.
METHODS: We conducted a retrospective study in two pediatric nephrology centers in Paris, France, including SDNS patients treated with RTX who developed ARA and subsequently received obinutuzumab.
RESULTS: Thirty-two patients (median age 4.1 years) were included, previously treated with a median of 2 RTX infusions (IQR 1-2). ARA were detected at 3.2 months (range 0-17), following a median depletion of 2.9 months (IQR 2.1-5.8); 13/32 had titers ≥ 100 ng/mL. Obinutuzumab was given for short/failed RTX depletion (n = 19) or early relapse (n = 13). Six infusion reactions occurred but no serum sickness. B-cell depletion after obinutuzumab lasted 6.5 months (IQR 5.6-8.1). Among 28 patients with baseline ARA at obinutuzumab infusion, 50% had titers ≥ 100 ng/mL, with no difference in B-cell depletion (median 5.3 vs. 6.8 months; p = 0.40), or relapse-free survival at 24 months (75% vs. 46%; p = 0.10). Longitudinal ARA monitoring showed sustained positivity in 76.5% at 6 months, and one patient > 100 ng/mL at 24 months.
CONCLUSION: Obinutuzumab is an effective and well-tolerated option in the context of ARA, providing prolonged B-cell depletion. Further studies with ARA monitoring are needed to optimize anti-CD20 therapy.
METHODS: We conducted a retrospective study in two pediatric nephrology centers in Paris, France, including SDNS patients treated with RTX who developed ARA and subsequently received obinutuzumab.
RESULTS: Thirty-two patients (median age 4.1 years) were included, previously treated with a median of 2 RTX infusions (IQR 1-2). ARA were detected at 3.2 months (range 0-17), following a median depletion of 2.9 months (IQR 2.1-5.8); 13/32 had titers ≥ 100 ng/mL. Obinutuzumab was given for short/failed RTX depletion (n = 19) or early relapse (n = 13). Six infusion reactions occurred but no serum sickness. B-cell depletion after obinutuzumab lasted 6.5 months (IQR 5.6-8.1). Among 28 patients with baseline ARA at obinutuzumab infusion, 50% had titers ≥ 100 ng/mL, with no difference in B-cell depletion (median 5.3 vs. 6.8 months; p = 0.40), or relapse-free survival at 24 months (75% vs. 46%; p = 0.10). Longitudinal ARA monitoring showed sustained positivity in 76.5% at 6 months, and one patient > 100 ng/mL at 24 months.
CONCLUSION: Obinutuzumab is an effective and well-tolerated option in the context of ARA, providing prolonged B-cell depletion. Further studies with ARA monitoring are needed to optimize anti-CD20 therapy.