A global antiB cell strategy combining obinutuzumab and daratumumab in severe pediatric nephrotic syndrome
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ORIGINAL ARTICLE
A global antiB cell strategy combining obinutuzumab and daratumumab in severe pediatric nephrotic syndrome Claire Dossier 1 & Benjamin Prim 1 & Christelle Moreau 2 & Thérésa Kwon 1 & Anne Maisin 1 & Sylvie Nathanson 3 & Christiane De Gennes 4 & Katia Barsotti 5 & Abdelmajid Bourrassi 6 & Julien Hogan 1 & Georges Deschênes 1 Received: 3 March 2020 / Revised: 18 September 2020 / Accepted: 2 October 2020 # IPNA 2020
Abstract Background Steroid-sensitive nephrotic syndrome (SSNS) is, in most patients, a chronic disease with 80% experiencing at least one relapse after first flare. B cell depletion using rituximab is effective in preventing relapse in steroid-dependent (SDNS) patients but fails to maintain long-term remission following B cell recovery, possibly due to development of autoreactive long-lived plasma cells. We investigated sequential combination of antiCD20 antibody targeting all B cell subsets, and antiCD38 antibody with high plasma cell cytotoxicity in patients with uncontrolled SDNS after failure of one or several attempts at B cell depletion. Methods Fourteen patients with median disease duration 7.8 years received 1000 mg/1.73 m2 obinutuzumab followed by 1000 mg/ 1.73 m2 daratumumab 2 weeks later. Oral immunosuppression was discontinued within 6 weeks, and biological monitoring performed monthly until B cell recovery. Results Median age at treatment was 11.0 [IQR 10.4–14.4] years. B cell depletion was achieved in all patients, and B cell reconstitution occurred in all at median 9.5 months after obinutuzumab injection. After median follow-up 20.3 months (IQR 11.5–22.6), 5/14 patients relapsed including 4 within 100 days following B cell repletion. Relapse-free survival was 60% at 24 months from obinutuzumab infusion. Mild infusion reactions were reported in 3/14 patients during obinutuzumab and 4/14 during daratumumab infusions. Mild transient neutropenia (500–1000/mm3) occurred in 2/14 patients. Intravenous immunoglobulins were given to 12/14 patients due to hypogammaglobulinemia. Low IgA and IgM levels were noted in 8 and 14 patients, respectively. No severe infection was reported. Conclusion Global antiB cell strategy combining obinutuzumab and daratumumab induces prolonged peripheral B cell depletion and remission in children with difficult-to-treat SDNS. Keywords Children . Steroid-dependent nephrotic syndrome . Rituximab . Relapse . Obinutuzumab . Daratumumab . B cell recovery
Background Although the majority of children with idiopathic nephrotic syndrome (INS) are steroid sensitive (SSNS), 80% of them
will experience relapses and a chronic evolution of the disease [1]. A significant proportion of frequent relapsers (FRNS) and steroid dependent (SDNS) will have a protracted course exceeding 10 years and be exposed to oral prednisone and
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00467-020-04811-0) contains supplementary material, which is available to authorized users. * Georges Deschênes [email protected] 1
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