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Updated: Aug 10, 2026
In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Anti-CD38/Anti-CD20 Rescue Therapy for Posttransplant Recurrent FSGS
Juliette Leon1, Elise Ducrocq1, Marie-Camille Lafargue1,2
1Department of Kidney Diseases and Metabolism, Transplantation and Clinical Immunology, Necker Hospital, Assistance Publique-Hôpitaux de Paris, and Université Paris Cité, Paris, France.
Introduction:
Recurrent focal segmental glomerulosclerosis (FSGS, 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; however, multicenter real-world data integrating clinical, biological, and histological characterization remain limited.
Methods:
We retrospectively studied 17 kidney transplant recipients with rFSGS treated with daratumumab (anti-CD38) administered after and/or in combination with anti-CD20 therapy across 12 French centers. Patients were clinically and histologically characterized at treatment initiation. Clinical response, safety, and longitudinal antinephrin 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 (CR) and 4 (24%) achieved partial remission (PR), allowing discontinuation of apheresis in all responders. Median response time 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, 3 had positive antinephrin antibodies. Two patients showed marked posttreatment declines paralleling clinical response, whereas 1 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 antinephrin antibodies in selected cases. Prospective trials are warranted to define optimal patient selection and dosing, and to clarify its place in therapy.
