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. 2025 Jul 15;10(10):3506-3515.
doi: 10.1016/j.ekir.2025.07.009. eCollection 2025 Oct.

Anti-CD38 Daratumumab Treatment of Chronic Active Antibody-Mediated Kidney Allograft Rejection

Wai-Choong Lye  1 , Hwai-Liang Loh  2
Affiliations

Anti-CD38 Daratumumab Treatment of Chronic Active Antibody-Mediated Kidney Allograft Rejection

Wai-Choong Lye et al. Kidney Int Rep. .

Abstract

Introduction: Chronic active (c) antibody-mediated rejection (ABMR) (cABMR) remains the leading cause of graft loss in kidney transplant recipients (KTRs). The efficacy of subcutaneous daratumumab, an anti-CD38 monoclonal antibody targeting plasma cells and natural killer (NK) cells, to treat cABMR was studied.

Methods: A retrospective chart review was performed on KTRs with cABMR diagnosed > 6 months after transplantation and treated with a flat dose of subcutaneous daratumumab 1800 mg weekly for 4 weeks followed by 3 quarterly doses. The patients were monitored before and after treatment using estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), renal-biopsy, donor-derived cell-free DNA (dd-cfDNA) and donor-specific antibody (DSA) levels. Adverse events were monitored.

Results: Sixteen KTR with cABMR (median time from transplantation to treatment: 9 years) were treated with daratumumab. No major adverse events occurred. After 10 months, biopsy histology showed improvement in microvascular inflammation scores in 13 of 16 patients and molecular ABMR scores decreased (median 74% decline), with 8 of 16 patients experiencing complete molecular remission of ABMR. eGFR levels remained stable, UACR improved in 11 of 16 patients and dd-cfDNA significantly decreased (median decrease: 85%). DSA became negative in 2 of 12 previously positive patients. After completion of treatment, patients were monitored quarterly with eGFR, UACR, and dd-cfDNA. Two patients showed recurrence of cABMR based on dd-cfDNA, were retreated, and showed stabilization/improvement.

Conclusion: Subcutaneous daratumumab may be an effective treatment for cABMR; larger randomized trials are warranted to study its role in the treatment for cABMR in KTRs. dd-cfDNA may be a useful monitoring tool to predict and detect relapses.

Keywords: anti-CD38 monoclonal antibodies; chronic active antibody-mediated rejection; kidney transplantation; retrospective chart review.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Timeline of daratumumab treatment and data collection. cABMR, chronic active antibody-mediated rejection; dd-cfDNA, donor-derived cell-free DNA; DSA, donor-specific antibody; MMDx, molecular microscope diagnostic.
Figure 2
Figure 2
Boxplots showing the median and interquartile biomarker results at the pre- and post-treatment time points for (a) molecular microscope diagnostic (MMDx) antibody-mediated rejection (ABMR) scores, (b) donor-derived cell-free DNA (dd-cfDNA) fraction, (c) estimated glomerular filtration rate (eGFR) levels, and (d) urine albumin-to-creatinine ratios (UACR).
Figure 3
Figure 3
Donor-derived cell-free DNA (dd-cfDNA) timeline for 2 patients with dd-cfDNA rebound, along with the daratumumab treatment windows and relevant biopsy results.
See this image and copyright information in PMC

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