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Abstract: SA-PO924

Efficacy of Combined Rituximab (Anti-CD20) and Daratumumab (Anti-CD38) in Steroid-Resistant Nephrotic Syndrome and in Post-Transplant Recurrent FSGS

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Angeletti, Andrea, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Bruschi, Maurizio, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Lugani, Francesca, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Verrina, Enrico E., Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Caridi, Gianluca, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • La Porta, Edoardo, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Kajana, Xhuliana, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Spinelli, Sonia, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Romagnani, Paola, University of Florence, Florence, Italy
  • Magnasco, Alberto, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Cravedi, Paolo, Mount Sinai Health System, New York, New York, United States
  • Ghiggeri, Gian Marco, Istituto Giannina Gaslini, Genova, Liguria, Italy
Background

Multidrug-resistant nephrotic syndrome (MRNS) accounts for 15% of overall cases of nephrotic syndrome (NS) in childhood. MRNS is associated with high risk of kidney failure and recurrence after kidney transplant (KT). Common treatments, including rituximab and plasma exchange (PEX), are poorly effective.

Methods

We ran a phase II proof-of concept clinical study (NCT05704400) including patients with MRNS (lack of antiproteinuric effect of therapy based on steroid plus CNI and MMF for at least 12 months before enrolment) and post-transplant FSGS recurrence (FSGSr) resistant to rituximab and PEX. We administered rituximab (single infusion 350mg/m2, i.v.) + daratumumab (single 16mg/kg infusion). Primary outcome was complete (CR) or partial remission (PR defined as >50% proteinuria reduction).

Results

We enrolled 8 patients: 5 with MRNS and 3 FSGSr (Fig.1a). MRNS resulted resistant to previous infusion of rituximab alone (last infusion at least 9 months before enrollment). Combined rituximab + daratumumab therapy induced CR or PR in 3 and 2 subjects with MRNS, respectively (Fig.1b). In one patient with older history of MRNS (5yrs), proteinuria remission was transient, but she refused a second treatment. All 3 FSGSr achieved CR/PR and PEX was stopped. Relapse occurred after 4 months in all pts. We repeated the combined treatment in 2 pts that after initial reduction, had a second relapse after 4 months. Thereafter, administration of daratumumab alone obtained remission as well (Fig.1c). Treatment was well tolerated and all patients are in active follow-up.

Conclusion

Combined treatment with rituximab and daratumumab is effective in inducing proteinuria remission in MRNS and FSGS recurrence. In KT, relapse-free time was 4 months and repeated infusions were needed. Therefore, targeting CD20 and CD38 may represent a valid therapeutic strategy in MRNS and FSGS recurrence.