ESPN 54th Annual Meeting

ESPN 2022


 
Daratumumab enables sustained remission after Immunoadsorption in refractory multidrug resistant nephrotic syndrome
CLAIRE DOSSIER 1 ANNE-LAURE LECLERC 2 MARC FILA 3 ROBERT NOVO 4 LISE ALLARD 5 THERESA KWON 1 JULIEN HOGAN 1

1- PEDIATRIC NEPHROLOGY, ROBERT-DEBRE HOSPITAL, APHP, PARIS
2- PEDIATRIC NEPHROLOGY, HOSPICES CIVILES DE LYON
3- PEDIATRIC NEPHROLOGY, CHU MONTPELLIER
4- PEDIATRIC NEPHROLOGY, CHU LILLE
5- PEDIATRIC NEPHROLOGY, CHU BORDEAUX
 
Introduction:

Multidrug Resistant Nephrotic Syndrome (MRNS) is a dramatically challenging condition that may lead to end-stage renal disease and post-transplant recurrence. Immunoadsorption of Immunoglobulins (IA) has been reported safe and efficient to induce remission, however most patients relapse after discontinuation, and some happen to be IA-dependent. Long-lived plasma-cells may be responsible for refractory NS. We report the use of Daratumumab(DARA), an antiCD38 monoclonal antibody that targets plasma cells, in IA-dependent MRNS.

Material and methods:

In this retrospective multicenter study, we included children with MRNS that reached complete remission after IA, but relapsed when lowering frequency of IA sessions despite B-cell depletion. We report on a further attempt of IA withdrawal adding 4 weekly infusions of daratumumab of 1000mg/1.73m2.

Results:

Four boys and 2 girls were included. Median age at diagnosis was 6.1 years (range 5.5-7.9). Renal biopsy showed FSGS in 3 patients and MCD in 3. All had negative genetic testing. All were resistant to ciclosporine and/or tacrolimus, 4 also received MMF and 3 rituximab(RTX). Median time between INS diagnosis and IA initiation was 1 year (0.5-5.6). All patients achieved complete remission after IA but relapsed after a first discontinuation attempt, despite B-cell depletion with RTX(n=3) or Obinutuzumab(OBI) (n=3). Complete remission was again obtained with intensive IA in all but one with partial remission. All patients received a new infusion of anti-CD20 (obinutuzumab) followed by 4 injections of daratumumab. Complete remission was sustained in all patients enabling IA withdrawal. Proteinuria relapsed in 4 patients (RPC 0.05-0.10g/mmol) and was successfully treated with either a single reinjection of daratumumab (n=2) or combined to OBI and/or IA. All patients were in complete remission at 7 months (range 1.5-17.5) following IA discontinuation. 

Conclusions:

The association of plasma-cell depletion with daratumumab to  B-cell depletion allowed IA discontinuation in all patients with Ig-IA dependent MRNS. Further studies are needed to confirm the efficacy of daratumumab in children with MRNS and better define its place in the treatment strategy.