Donor-Derived Cell-Free DNA as a Marker for the Efficacy of Daratumumab in Patients With Antibody-Mediated Rejection Post-Heart Transplantation: A Case Series.

Background: Antibody-mediated rejection (AMR) remains a significant complication following heart transplantation, contributing to graft dysfunction and reduced survival. Donor-derived cell-free DNA (dd-cfDNA) is emerging as a non-invasive biomarker for detecting and monitoring graft injury, correlating with episodes of rejection and response to treatment. Daratumumab, an anti-CD38 monoclonal antibody targeting plasma cells, has shown promise in treating AMR. We present a case series of pediatric and young adult heart transplant recipients demonstrating donor-derived cell-free DNA's potential utility in monitoring for AMR and the effect of therapies including daratumumab.

Case descriptions: We report five cases showing that elevated dd-cfDNA correlated with pathological AMR (pAMR), and treatment with daratumumab improved both pAMR and dd-cfDNA levels. Most of our patients had persistently elevated donor-specific antibody (DSA) as observed by MFI values; however, there was a reduction in DSA titer that corresponded with improvement in pAMR and dd-cfDNA levels. Recurrent increases in dd-cfDNA were also useful in guiding the need for repeat treatment with daratumumab. Although DSA levels often remained elevated despite histologic improvement, decreasing dd-cfDNA levels correlated more closely with the resolution of AMR.

Conclusion: In this case series of pediatric and young adult heart transplant recipients, our findings suggest that dd-cfDNA can serve as a valuable biomarker for diagnosing AMR and treatment response, which are not often reflected by DSA MFI alone. Our dd-cfDNA data supports the efficacy of daratumumab in treating AMR and may guide the need for ongoing treatment. Further studies are warranted to validate these findings and establish guidance for the use of daratumumab and dd-cfDNA in this patient population.