Daratumumab for Non-Acute Antibody-Mediated Rejection After Pediatric Heart Transplantation: Treatment…

Cohort studyThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation· Aug 2026

Daratumumab for Non-Acute Antibody-Mediated Rejection After Pediatric Heart Transplantation: Treatment Response in the Presence and Absence of Circulating HLA Donor-Specific Antibody.

Yuen Lo Yau Leung, Qingyong Xu, Matthew D Zinn … Brian Feingold

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Transplant & Mechanical SupportCohort studyTreatmentQ1IF 5.5

Daratumumab was associated with a sharp drop in donor-derived cell-free DNA in antibody-mediated rejection.

Daratumumab for Non-Acute Antibody-Mediated Rejection After Pediatric Heart Transplantation: Treatment Response in the Presence and Absence of Circulating HLA Donor-Specific Antibody.

Yuen Lo Yau Leung … Brian Feingold

The Journal of heart and lung transplantation · Aug 2026 · Q1 in Respiratory Medicine

Background

Late graft survival after pediatric heart transplantation (heart transplantation) remains inadequate, with chronic rejection being a major contributor.

Methods

We retrospectively analyzed all heart transplantation recipients at our center treated with daratumumab (16 mg/kg × 4 doses) for antibody-mediated rejection identified by elevated donor-derived cell-free DNA (dd-cfDNA) without graft dysfunction or hemodynamic compromise and confirmed by endomyocardial biopsy gene expression profiling (endomyocardial biopsy gene expression profiling).

n = 6

Results

daratumumab nearly eliminated donor DNA in the blood, signaling rejection resolution

Pre-treatment dd-cfDNA

1.6%

Post-treatment dd-cfDN

0.04%

More results

Among 8 with post-treatment EMB, antibody-mediated rejection resolved (n=6) or showed only possible antibody-mediated rejection (n=2) after treatment.

HLA-DSA total MFI (p=0.031), non-HLA antibody burden (p=0.004), and AT1R Ab concentration (p=0.004) declined post-treatment.

More results

Six patients experienced subsequent elevations of dd-cfDNA at a median of 246 days (IQR, 239-283) with antibody-mediated rejection recurrence on EMB and responded to retreatment.

No T-cell mediated rejection occurred after treatment.

“

Conclusion · 1 of 3

Daratumumab was associated with significant improvements in dd-cfDNA, endomyocardial biopsy gene expression profiling, and antibody burden in pediatric and young adult heart transplantation recipients with antibody-mediated rejection.

Conclusion · 2 of 3

Response among patients without circulating HLA-DSA or with reduced but persistent HLA-DSA after treatment implies effects beyond plasma cell depletion.

Conclusion · 3 of 3

Rebound antibody-mediated rejection was common but responded to retreatment, suggesting periodic maintenance dosing may be required. Prospective studies are needed to define optimal treatment strategies and long-term outcomes.

Daratumumab for Non-Acute Antibody-Mediated Rejection After Pediatric Heart Transplantation: Treatment Response in the Presence and Absence of Circulating HLA Donor-Specific Antibody.

Daratumumab for Non-Acute Antibody-Mediated Rejection After Pediatric Heart Transplantation: Treatment Response in the Presence and Absence of Circulating HLA Donor-Specific Antibody.

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