Daratumumab for Anti-HLA Antibody Desensitization and Antibody Mediated Rejection in Pediatric Heart Transplant Patients.

BACKGROUND

Pediatric heart transplant recipients have high rates of alloantibody development and antibody-mediated rejection (AMR). Daratumumab is a novel therapy that targets plasma cells and has been utilized in transplant populations, but data in pediatric populations are limited. Here, we describe the utilization of daratumumab in pediatric heart transplant recipients.

METHODS

Twelve patients at a single institution were treated with daratumumab for AMR (n = 9) or anti-HLA antibody desensitization (n = 3). Three doses of daratumumab were administered with additional doses based on clinical response. For AMR, response to daratumumab was evaluated based on hemodynamics, histopathology, biopsy mRNA expression profiling, ejection fraction, donor-specific antibody titers, and donor-derived cell-free DNA fraction. For desensitization, cPRA pre- and post-daratumumab were reported.

RESULTS

Sixty-five daratumumab infusions were administered to 12 patients (age 0.5-24 years; weight 8-90 kg). Infusion reactions occurred in 12% of infusions; however, none required discontinuation. Nine patients (75%) experienced infection; most were common childhood infections and did not require hospitalization. All 9 AMR patients showed improvement in AMR, and those with chronic AMR benefitted from repeat daratumumab administration. All desensitization patients had dramatic declines in cPRA, and two underwent successful transplantation without rejection 9 months post-transplant.

CONCLUSIONS

We report that daratumumab is safe and effective in a small series of pediatric heart transplant patients, including patients as young as 6 months old. Daratumumab could prove to be a valuable tool for desensitization and AMR treatment; however, additional studies are needed to corroborate these findings and determine long-term outcomes.