(217) Successful Desensitization of HLA and Non-HLA Antibody with daratumumab-based Immunotherapy: A case report from pediatric cardiac transplantation

Body: Pediatric heart transplant (HT) candidates often experience frequent sensitization events during congenital heart disease palliation prior to HT, contributing to high waitlist (WL) mortality. Here, we present a pediatric HT case with successful desensitization of antibodies to both human leukocyte antigens HLA and non-HLA antigens. A 16-month-old male was listed for HT due to end-stage heart failure secondary to congenital heart disease. Upon listing, the patient had a strong PRA level of 97% (cutoff: ≥4000 MFI) and multiple non-HLA antibodies (NHAB) detected via LABScreen™ HLA Class I/II, LABScreen™ Autoantibody, and EIA-AT1RX assays (Thermo Fisher Scientific). Initial desensitization included one dose of rituximab, four doses of bortezomib, and a single dose of IVIG (2 g/kg), followed by four weekly doses of daratumumab. This regimen reduced PRA to 95% after 8 weeks on the WL. Continued treatment with four biweekly doses of daratumumab and two additional doses of IVIG further reduced PRA to 86%, and ultimately to 0%, along with NHABs becoming undetectable, except for borderline-positive antibody to angiotensin II type 1 receptor, by week 20 on the WL. PRA remained at 0% until HT (Figures 1 and 2). The patient underwent HT at 33 weeks on the WL with a negative flow cytometry crossmatch and borderline allelic DR53 donor-specific antibody (DSA). Post-transplant antibody monitoring revealed that NHABs remained negative (Data not shown); however, weak DQ6 and borderline DR53 DSAs rebounded on post-operative day (POD) 13 and peaked on POD16 with DQ6 - 9239 Mean Fluorescence Intensity (MFI) and DR53 - 2540 MFI. Administration of IVIG and rituximab post-HT effectively reduced DSAs to negative (Figure 3).

Conclusion: Daratumumab-based desensitization therapy can remarkably reduce both HLA and non-HLA antibodies, potentially expanding donor access for highly sensitized pediatric HT candidates. However, due to the risk of memory immune responses triggered by HT-mismatched antigens, close post-HT DSA monitoring and timely therapeutic intervention are essential to prevent antibody-mediated rejection and subsequent graft failure.