Anti-CD38 Daratumumab Treatment of Chronic Active Antibody-Mediated Kidney Allograft Rejection
In a retrospective series of 16 kidney transplant recipients with chronic active antibody-mediated rejection, subcutaneous daratumumab was associated with improved microvascular inflammation, large declines in molecular ABMR activity and donor-derived cell-free DNA, and stable graft function, supporting further randomized study.
Background
Chronic active antibody-mediated rejection (cABMR) remains the leading cause of graft loss in kidney transplant recipients, and current therapies have inconsistent efficacy. Daratumumab is an anti-CD38 monoclonal antibody that targets plasma cells and natural killer cells, both implicated in the pathophysiology of antibody-mediated rejection.
Study design
This was a retrospective chart review of 16 kidney transplant recipients with cABMR diagnosed more than 6 months after transplantation (median time from transplantation to treatment, 9 years). Patients received a flat dose of subcutaneous daratumumab 1,800 mg weekly for 4 weeks followed by 3 quarterly doses, and were monitored with eGFR, urine albumin-to-creatinine ratio, renal biopsy, donor-derived cell-free DNA, and donor-specific antibody levels.
Key findings
After 10 months, biopsy histology showed improved microvascular inflammation scores in 13 of 16 patients, and molecular ABMR scores fell by a median of 74%, with 8 of 16 achieving complete molecular remission. eGFR remained stable, urine albumin-to-creatinine ratio improved in 11 of 16, and donor-derived cell-free DNA decreased by a median of 85%. Donor-specific antibody became negative in 2 of 12 previously positive patients, and no major adverse events occurred. Two patients had recurrence detected by donor-derived cell-free DNA and stabilized after retreatment.
Clinical implications
Subcutaneous daratumumab may be an effective treatment for chronic active ABMR, and donor-derived cell-free DNA may serve as a useful tool to monitor response and detect relapse. Because this is an uncontrolled retrospective series, larger randomized trials are warranted to define daratumumab's role in transplant rejection.
Category
Transplant
Source
Kidney International Reports
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