Open-Label Phase 1/2 Study of Daratumumab-Based Desensitization Before Kidney Transplantation

Area of Science:

• Nephrology
• Immunology
• Transplantation

Background:

• Kidney transplantation is crucial for end-stage renal disease.
• Highly sensitized patients with high calculated panel reactive antibody (cPRA) face significant challenges.
• Anti-CD38 monoclonal antibodies like daratumumab offer potential for desensitization.

Purpose of the Study:

• To evaluate the safety and efficacy of daratumumab for desensitization in kidney transplant candidates.
• To assess the reduction in anti-human leukocyte antigen (HLA) antibodies and cPRA.
• To monitor immune cell populations and adverse events.

Main Methods:

• A 2-phase (1 and 2), monocentric open-label study.
• Phase 1: Escalating doses of daratumumab.
• Phase 2: 8 weekly infusions of 16 mg/kg daratumumab in patients with cPRA > 95%.

Main Results:

• No serious treatment-emergent adverse events (TEAEs) were observed; mild TEAEs were mostly infusion-related.
• Significant reductions in anti-HLA antibodies and cPRA were seen by month 3.
• Durable response (cPRA decrease) at month 6 was achieved in 76.92% for cPRA > 10,000, but returned to baseline by month 12.

Conclusions:

• Daratumumab demonstrates initial safety and transient efficacy in desensitizing highly sensitized kidney transplant candidates.
• Infusion-related adverse events were common.
• The limited durability of antibody reduction restricts its widespread clinical application in this context.