Daratumumab Therapy for Antibody-Mediated Rejection in Heart Transplant Patients

Introduction to Daratumumab Therapy

The American Heart Association recognizes daratumumab as a reasonable secondary therapy for AMR in heart transplant recipients (Class IIa; Level of Evidence C), particularly for refractory cases where first-line therapies have been insufficient 3, 4
Daratumumab uniquely targets CD38-expressing plasma cells, which are the primary producers of donor-specific antibodies—a critical advantage since these long-lived plasma cells do not express CD20 and therefore cannot be targeted by rituximab 5, 1

The proposed treatment protocol (8 weekly doses, followed by 8 doses every other week, then monthly starting at week 25) aligns with established transplant center protocols for AMR management 3, 4
The combination of IVIG with daratumumab for AMR management is specifically outlined in American Heart Association treatment protocols 3, 4, 2

Common side effects include infusion-related reactions (occurring in approximately 27-28% of patients), secondary hypogammaglobulinemia requiring monitoring, and increased infection risk 6
Regular assessment of DSA levels, immunoglobulin levels, and follow-up endomyocardial biopsies are necessary to evaluate treatment response and guide therapy duration 2

First-line therapy (methylprednisolone, IVIG, plasmapheresis) → Second-line plasma cell-directed therapy (daratumumab) represents the evidence-based treatment escalation for AMR 3, 4, 1
This treatment is medically necessary to prevent graft loss and mortality in a patient with biopsy-proven AMR and high-titer DSAs following recent heart transplantation 3, 4, 1, 2