ESPN 53rd Annual Meeting

ESPN 2021


 
Rituximab bioavailability in pediatric patients with steroid dependent idiopathic nephrotic syndrome
CYRIELLE PARMENTIER 1 SABINE MIGNOT 2 QUENTIN BERTRAND 3 TIM ULINSKI 1 CLAIRE DOSSIER 4

1- TROUSSEAU HOSPITAL, PARIS FRANCE
2- BICHAT HOSPITAL, PARIS, FRANCE
3- CLINIQUE CHC, LIEGE, BELGIQUE
4- ROBERT DEBRE HOSPITAL, PARIS FRANCE
 
Introduction:

B-cell depletion is an efficient treatment option in pediatric patients with steroid dependent idiopathic nephrotic syndrome (SDNS). Despite overall satisfying results concerning tolerance and remission maintenance, some patients experience rapid relapses and/or had a short B-cell depletion with rituximab (RTX) infusions.

Material and methods:

We aim to analyze the RTX bioavailability, evaluate the presence of anti-RTX antibodies (ARA) and measured RTX serum levels monthly in 43 pediatrics patients with SDNS treated with an injection of 375mg/m2 RTX, of which, 24 patients received a first RTX.

Results:

The median B-cell depletion was 3.8 months (IQ 2.8; 4.5). RTX serum level 1 month (M1) post RTX injection were significantly lower for the 7 patients with a short B cell depletion period (< 3 months), 0 µg/ml (IQ 0 ; 6,2) vs. 34 µg/ml (IQ 22,8 ; 37) for the others (p<0.0001).
ARA were detected in 11 patients (26%) during follow-up. Among the 5 patients with ARA after the first RTX, all achieved B-cell depletion, with a median duration of 3.0 months (IQ 2.7; 3.8). Furthermore, 4 out of 6 patients with ARA after the second or more RTX, did not achieve B-cell depletion, and developed ARA at baseline or M1 after these RTX. Seven of the 11 patients ARA+ were switched to obinutuzumab and achieved complete B-cell depletion with a median duration of 7.6 months (IQ 5.9 ; 9.01) suggesting that ARA do not have any cross-reactivity against obinutuzumab.

Conclusions:

ARA should be searched for in patients with short or absent B-cell depletion following RTX treatment.  The use of obinutuzumab seems to cover the specific needs in these patients. ARA and RTX serum levels are of interest in order to individualize the use of B-cell depleting agents in patients with “difficult-to treat” SDNS.