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Background <p>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.</p> Methods <p>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.</p> Results <p>Thirty-two patients (median age 4.1&#xa0;years) were included, previously treated with a median of 2 RTX infusions (IQR 1–2). ARA were detected at 3.2&#xa0;months (range 0–17), following a median depletion of 2.9&#xa0;months (IQR 2.1–5.8); 13/32 had titers ≥ 100&#xa0;ng/mL. Obinutuzumab was given for short/failed RTX depletion (<i>n</i> = 19) or early relapse (<i>n</i> = 13). Six infusion reactions occurred but no serum sickness. B-cell depletion after obinutuzumab lasted 6.5&#xa0;months (IQR 5.6–8.1). Among 28 patients with baseline ARA at obinutuzumab infusion, 50% had titers ≥ 100&#xa0;ng/mL, with no difference in B-cell depletion (median 5.3 vs. 6.8&#xa0;months; <i>p</i> = 0.40), or relapse-free survival at 24&#xa0;months (75% vs. 46%; <i>p</i> = 0.10). Longitudinal ARA monitoring showed sustained positivity in 76.5% at 6&#xa0;months, and one patient &gt; 100&#xa0;ng/mL at 24&#xa0;months.</p> Conclusion <p>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.</p> Graphical abstract <p></p>

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Obinutuzumab as a therapeutic option for SDNS children resistant to rituximab with anti-RTX antibodies

  • 期刊论文

  • 发表日期：

    2025年11月14日

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  • Cyrielle Parmentier,
  • Anne-Lise Mary,
  • Antoine Diep,
  • Julien Hogan,
  • Tim Ulinski,
  • Sabine Mignot,
  • Claire Dossier

摘要

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.

Graphical abstract