Anti-CD38/Anti-CD20 Rescue Therapy for Post-Transplant Recurrent Focal Segmental Glomerulosclerosis

Introduction Recurrent focal segmental glomerulosclerosis (rFSGS) is a severe complication after kidney transplantation, often resistant to standard therapies and requiring prolonged apheresis. Combined depletion of plasma cells (anti-CD38) and B cells (anti-CD20) has emerged as a potential strategy, but multicenter real-world data integrating clinical, biological, and histological characterization remain limited. Methods We retrospectively studied 17 kidney transplant recipients with rFSGS treated across 12 French centers with daratumumab (anti-CD38) administered after and/or in combination with anti-CD20 therapy. Patients were clinically and histologically characterized at treatment initiation. Clinical response, safety, and longitudinal anti-nephrin antibody trajectories were assessed. Results Median time from recurrence to daratumumab initiation was 5 months. All patients had previously received B-cell-depleting therapy. After the first daratumumab course (1-8 injections), 7 patients (41%) achieved complete remission and 4 (24%) partial remission, allowing discontinuation of apheresis in all responders. Median time to response was 24 days. During a median follow-up of 8 months, 3 responders relapsed but regained remission after retreatment. Median proteinuria decreased from 3.9 g/g to 1.4 g/g at 1 month (p=0.029). Among 11 patients tested, three had positive anti-nephrin antibodies. Two patients showed marked post-treatment declines paralleling clinical response, whereas one did not. Treatment was well tolerated. Conclusion In this multicenter real-world cohort, combined plasma cell and B-cell depletion was associated with meaningful remission rates in refractory rFSGS and was accompanied by dynamic changes in anti-nephrin antibodies in selected cases. Prospective trials are warranted to define optimal patient selection and dosing, and to clarify its place in therapy.