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Combined Anti-CD20/Anti-CD38 Therapy in Posttransplant Focal Segmental Glomerulosclerosis Recurrence: A
Paolo Cravedi1, Umberto Maggiore2, Gabriele Mortari3
1Department of Medicine, Transplantation Research Center, Icahn School of Medicine at Mount Sinai, New York, NY.
Background:
Focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation is a leading cause of allograft failure and remains difficult to treat. Standard therapies, including plasma exchange (PEX) and rituximab, are often ineffective and poorly tolerated. Growing evidence implicates immune-mediated circulating factors, such as IgG and IgM autoantibodies, in disease pathogenesis. Given the central role of memory B cells and plasma cells in antibody production, we tested the safety/efficacy profile of a combined B-cell and plasma cell-depleting approach with rituximab and daratumumab in patients with posttransplant FSGS recurrence.
Methods:
This is a retrospective analysis of a multicenter, international cohort of sixteen patients (median age 37 y) with biopsy-proven FSGS recurrence posttransplant who received anti-CD20 plus anti-CD38 monoclonal antibodies or anti-CD38 alone. The majority of patients were resistant to common therapies, including rituximab and PEX.
Results:
The treatment achieved complete or partial remission in 5 and 11 patients, respectively. Five experienced proteinuria relapse, and 4 responded to repeated daratumumab alone. At the last follow-up (median 11 [2-18] mo), 13 patients are still in remission and PEX was discontinued in all but 3 cases. Overall, kidney function improved after treatment, and no severe acute or chronic adverse events were reported. Serological analysis revealed a significant decline in IgM, but not in IgG, after treatment.
Conclusions:
Despite the retrospective, nonrandomized design, the temporal association between treatment and remission supports an effect of anti-CD38 monoclonal antibody alone or in combination with anti-CD20. Treatment is safe and may confer enhanced efficacy over standard approaches. Prospective, mechanistic studies are warranted to validate these findings and delineate the immunopathogenesis of FSGS recurrence.
Insights
A new treatment combining B-cell and plasma cell depletion shows promise for post-transplant Focal Segmental Glomerulosclerosis (FSGS) recurrence. This approach, using daratumumab with or without rituximab, achieved remission in most patients, offering a safer and potentially more effective alternative to standard therapies.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- Focal segmental glomerulosclerosis (FSGS) recurrence post-kidney transplant is a major cause of graft loss.
- Standard treatments like plasma exchange (PEX) and rituximab often fail and are poorly tolerated.
- Immune factors, including autoantibodies, are implicated in FSGS pathogenesis, highlighting the role of B cells and plasma cells.
Purpose of the Study:
- To evaluate the safety and efficacy of a combined B-cell and plasma cell-depleting therapy for post-transplant FSGS recurrence.
- To assess the impact of rituximab (anti-CD20) and daratumumab (anti-CD38) on patients resistant to conventional treatments.
Main Methods:
- Retrospective analysis of a multicenter, international cohort of 16 patients with biopsy-proven FSGS recurrence.
- Patients received anti-CD20 plus anti-CD38 monoclonal antibodies or anti-CD38 alone.
- Majority of patients had prior resistance to rituximab and PEX.
Main Results:
- Complete or partial remission was achieved in 16 out of 16 patients (5 complete, 11 partial).
- 13 patients remained in remission at median 11-month follow-up; PEX was discontinued in most.
- Kidney function improved, and no severe adverse events were reported. IgM levels decreased significantly post-treatment.
Conclusions:
- The combination of anti-CD20 and anti-CD38 monoclonal antibodies, or anti-CD38 alone, appears safe and effective for FSGS recurrence.
- This treatment may offer superior efficacy compared to standard therapies.
- Further prospective studies are needed to confirm findings and understand the immunopathogenesis.
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