Daratumumab combined with anti-CD20 therapy in pediatric and adult refractory idiopathic nephrotic syndrome: single-center experience.

Background: Refractory idiopathic nephrotic syndrome (INS), in native kidneys or post-transplant, represents a major therapeutic challenge due to its high risk of progressing to end-stage renal disease. Patients often resist anti-CD20 therapy and require prolonged apheresis. Daratumumab, an anti-CD38 monoclonal antibody targeting plasma cells, has demonstrated promising efficacy in case reports when combined with anti-CD20, but evidence remains limited. Methods: We conducted a single-center retrospective study including four patients (two pediatric, two adult, including one renal transplant) with INS refractory to conventional therapies (corticosteroids, calcineurin inhibitors, mycophenolate mofetil, anti-CD20 antibodies, and/or apheresis). All Patients received daratumumab combined with anti-CD20 therapy at University Hospital of La Réunion between 2022 and 2025. Clinical and laboratory data were extracted from medical records. Renal response was defined as complete remission (CR) or partial remission (PR). Results: The mean patient age was 20 ± 13 years (range: 8-40), with a male-to-female ratio of 3:1. Median follow-up after daratumumab administration was 5 months (range: 2-12). All patients achieved CR with a median time to response of 25 days (range: 14-30). Previously apheresis-dependent patients were able to discontinue sessions. Two patients developed infections (herpetic and SARS-CoV-2 pneumonia complicated by pneumococcal bacteremia), all resolving favorably. Renal function remained stable. Conclusion: Combined daratumumab and anti-CD20 therapy appears to be an effective rescue strategy for refractory INS, in native kidneys and post-transplant. It induces rapid and sustained remission, enabling discontinuation of apheresis. Prospective studies are warranted to optimize treatment regimens and identify predictive biomarkers of response.