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. 2023 Dec 1;18(12):1555-1562.
doi: 10.2215/CJN.0000000000000288. Epub 2023 Sep 6.

Obinutuzumab in Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome in Children

Claire Dossier  1 , Stéphanie Bonneric  1 , Véronique Baudouin  1 , Thérésa Kwon  1 , Benjamin Prim  1 , Alexandra Cambier  1 , Anne Couderc  1 , Christelle Moreau  2 , Georges Deschenes  1 , Julien Hogan  1   3
Affiliations

Obinutuzumab in Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome in Children

Claire Dossier et al. Clin J Am Soc Nephrol. .

Abstract

Background: B-cell depletion with rituximab induces sustained remission in children with steroid-dependent or frequently relapsing nephrotic syndrome. However, most patients relapse after B-cell recovery, and some patients do not achieve B-cell depletion. Obinutuzumab is a second-generation anti-CD20 antibody designed to overcome such situations in B-cell malignancies and was recently reported to be safe and effective in other autoimmune diseases affecting the kidneys.

Methods: We retrospectively report 41 children with steroid-dependent or frequently relapsing nephrotic syndrome treated with a single low-dose infusion of obinutuzumab at Robert-Debre Hospital between April 2018 and December 2020. Participants were treated because of rituximab resistance or relapse after rituximab and received a single infusion of 300 mg/1.73 m 2 obinutuzumab with cessation of oral immunosuppressors within 2 months.

Results: B-cell depletion was achieved in all participants and lasted a median of 8.3 months (interquartile range, 6.4-11.1), a duration exceeding that for last rituximab treatment. At 12 and 24 months, 92% (38/41) and 68% (28/41) of patients, respectively, were in sustained remission. Mild infusion reactions occurred in five participants (12%) and neutropenia in nine (21%). No significant decrease in IgG level was reported during treatment, and whereas IgM levels decreased in 34 patients (83%), they were normal at last follow-up in 32 (78%).

Conclusions: These results identified low-dose obinituzumab as a promising treatment option in children with steroid-dependent or frequently relapsing nephrotic syndrome, including those resistant to rituximab. The tolerance profile of obinutuzumab was similar to that of rituximab, but hemogram and immunoglobulin levels should be monitored.

Trial registration: ClinicalTrials.gov NCT05039619 NCT04629248 NCT04983888 NCT05786768 NCT05627557.

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Conflict of interest statement

S. Bonneric's husband reports employment with Abbvie (2020–2023) and MSD (2023–present). A. Cambier reports other interests or relationships with IgANN, IPNA, and SNP. J. Hogan reports consultancy for Alnylam, Biocodex, Novartis, and Traverse and research funding from CareDx. All remaining authors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Duration of B-cell depletion after a single low dose of obinutuzumab (300 mg/1.73 m2). (A) Cumulative incidence of B-cell repletion in n=41 patients and (B) according to the indication for obinutuzumab: absence or short duration of B-cell depletion <3 months (n=14, presented as “rituximab resistance”) or relapse following B-cell repletion after rituximab treatment (n=27, presented as “rituximab relapse”).
Figure 2
Figure 2
Relapse-free survival after a single low dose of obinutuzumab (300 mg/1.73 m2). Kaplan–Meyer of relapse-free survival is presented (A) in the total population of n=41 and (B) according to the indication for obinutuzumab: absence or short duration of B-cell depletion <3 months (n=14, presented as “rituximab resistance“) or relapse following B-cell repletion after rituximab treatment (n=27, presented as “rituximab relapse”). There was no significant difference between groups (log rank P = 0.2).
Figure 3
Figure 3
Stable IgG levels and transient IgM decrease in children treated with low-dose obinutuzumab. Serum levels of IgG (A), IgA (B), and IgM (C) at time points up to 24 months after obinutuzumab. Box and whiskers plots showing the median, interquartile range, and range. Normal Ig levels for 10-year-old children (i.e., the median age at obinutuzumab infusion in the study cohort) are shown. Data obtained during relapse or an additional course of anti-CD20 mAb were excluded, as were IgG levels for patients with IgIV supplementation.
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References

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