Daratumumab in Antibody-Mediated Rejection After Kidney Transplantation: Mechanistic Rationale, Published Clinical Experience, and a Single-Center Case Series.
Abstract
Background
Antibody-mediated rejection (AMR), driven by donor-specific antibodies (DSAs), remains a major cause of kidney allograft dysfunction. Conventional therapies reduce circulating antibodies and target precursor B cells but often fail to eliminate long-lived plasma cells, contributing to persistent or recurrent DSAs. CD38 is highly expressed on antibody-secreting cells, making it a selective therapeutic target for plasma cell depletion. Daratumumab, a fully human anti-CD38 IgG1κ monoclonal antibody, mediates depletion of CD38-expressing cells.
Objectives
Summarize the mechanistic rationale of daratumumab, review published experience with daratumumab in kidney transplantation, and describe a single-center experience using daratumumab for early, refractory AMR.
Methods
We conducted a narrative review of CD38 targeting in AMR and evaluated a retrospective single-center case series of kidney transplant recipients (KTRs) treated with daratumumab after suboptimal response to institutional first-line therapy. Kidney allograft biopsy findings, DSA trajectories, and renal function parameters were trended during follow-up. This study complied with the Declaration of Helsinki and the Declaration of Istanbul; no organs were procured from prisoners or paid donors.
Results
Two highly sensitized KTRs developed early acute AMR with persistent DSAs despite first-line therapies. Repeat biopsies demonstrated chronic active AMR (Patient 1) and ongoing/smoldering AMR (Patient 2). Subcutaneous daratumumab was initiated in both patients and there was a durable reduction in DSAs and stabilization or improvement in allograft function.
Conclusions
Daratumumab may serve as an adjunctive option for refractory AMR with persistent DSAs by targeting plasma cell-mediated alloantibody production. Prospective studies are required to define optimal dosing, timing, safety monitoring, and patient selection.