ESPN 50th Annual Meeting

ESPN 2017


 
LONG-TERM EFFECT OF RITUXIMAB TREATMENT: TWO SIDES OF THE SAME COIN
MANUELA COLUCCI 1 LAURA MASSELLA 1 ANTONIO GARGIULO 1 JESSICA SERAFINELLI 1 FRANCESCO EMMA 1 MARINA VIVARELLI 1

1- OSPEDALE PEDIATRICO BAMBINO GESù - IRCCS
 
Introduction:

 Rituximab (RTX), an anti-CD20 antibody, is effective in pediatric idiopathic nephrotic syndrome (INS). However, memory B cell subsets remain significantly reduced with long-term immunological impairment.

Material and methods:

B cell subsets were assessed by flow cytometry in 26 steroid-dependent INS children, with a minimum of 5 years after the 1st RTX infusion. For some patients levels of total immunoglobulins and of specific immunoglobulins to Measles, Tetanus, and Hepatitis B were assessed. At baseline, all patients were in remission on prednisone and 1 or 2 steroid-sparing agents (calcineurin inhibitors and mycophenolate mofetil). An initial dose of RTX (375 mg/m2), repeated at 7 days in case of incomplete depletion of B cells, was administered. All patients tapered concomitant immunosuppression. 

Results:

 Seven patients maintained complete remission during the entire follow-up. All other patients relapsed. Ten patients were retreated with RTX and 2 patients maintained complete remission after the 2nd RTX infusion whereas the others relapsed. Survival analysis showed a significantly delayed time to relapse (p=0.015) comparing 2nd to 1st RTX infusion. Three patients were retreated with a 3rd RTX infusion and relapsed. At last follow-up, immunosuppression was significantly reduced compared to baseline (0.7±1 vs 2.7±0.5, p<0.001) and all patients were in remission. Total CD19+ cells were recovered, but 21 patients still showed reduced switched memory B cells (<1.1% of total lymphocytes). Nine/20 patients showed reduced levels of IgG (<700 mg/dl) and 6/20 hypogammaglobulinemia (<480 mg/dl). Interestingly, low levels of IgG and/or IgA were observed in 3/5 non-relapsers after just one RTX infusion. Regarding vaccine response, we observed that only 4/19 patients resulted positive for anti-Hepatitis B IgG, 6/14 for anti-Measles IgG, and 3/11 for anti-Tetanus IgG. 

Conclusions:

 Although RTX treatment is an effective therapy for pediatric INS, it may have long-lasting effects on their immune memory also following a single RTX infusion.