Aim: Antibody-mediated rejection (AMR) in heart transplant recipients (HTR) remains a significant contributor to allograft failure and patient death. Treatment for AMR is often difficult and of limited effectiveness. Here, we summarize our experience using daratumumab, an anti-CD38 monoclonal antibody, for treating AMR in pediatric and young adult HTR. We analyzed the impact of daratumumab treatment on the reduction of donor-specific HLA antibodies (DSA) and non-HLA antibodies (Abs).
Methods: We retrospectively reviewed HTR treated with daratumumab for AMR at our pediatric center (16mg/kg x 4 IV for 10 weeks). DSA was tested prospectively with Luminex SAB (One lambda) using MFI>1000 as a positive cutoff. Additional dilutions were done for the strong DSAs (MFI>8000). The pre- and post-treatment sera were tested retrospectively for 60 non-HLA antibodies with a Luminex bead assay (Werfen). Positive non-HLA Abs were determined with vendor-provided thresholds.
Results: Seven patients received daratumumab for AMR between 11/2023 and 1/2025. Median age at HT was 10.2 yrs (18d–25.4 yrs) and at daratumumab was 17.1 yrs (7.7–27.2 yrs). AMR was diagnosed by histopathology (pAMR1h in 6 of 7), and by a biopsy gene expression profiling system (MMDx) in 7 of 7. All had positive dd-cfDNA (median 1.3%, 0.43%–5.0%) before treatment and declined after treatment. Four had positive DSAs before treatment, and the remaining three did not (Table 1). Daratumumab treatment reduced the MFI of DSAs by 81.9% ± 46.3% (range 38.7%–96.4%). All patients had between 1 and 5 non-HLA Abs before treatment. The number of positive non-HLA Abs was reduced in each patient after treatment (range 0–2). The MFI of the positive non-HLA Abs was notably lower after treatment in each patient (mean reduction 66% ± 22%). In the three cases without detectable DSAs (#5-7), the MFIs for non-HLA Abs were reduced by 23% to 79%. The most frequent non-HLA Abs are anti-CSF2 (granulocyte-macrophage colony-stimulating factor, 5/7) and anti-SSB (Sjögren syndrome antigen B, 4/7).
Conclusion: Daratumumab treatment for AMR significantly reduced DSA, some of which were at high titer. The number of positive non-HLA Abs and their MFIs were also reduced in all patients, including 3 of 7 with AMR in the absence of HLA DSA. Those findings support monitoring both non-HLA Abs and HLA DSA following AMR treatment.
