Aim: Daratumumab, an IgG kappa monoclonal antibody targeting CD38 antigen, has been considered a novel therapy in solid organ transplantation. Targeting CD38+ positive plasma cells, we hypothesize Daratumumab can decrease the mean fluorescence intensity of high titer anti-HLA antibodies detected in the recipient serum post transplant.
Method: In total we had 28 pediatric patients who had completed courses of Daratumumab for a variety of indications: oncological/hematological (N=14), Lung Transplant (N=2), Liver Transplant (N=1), Heart Transplant (N=11) and were reviewed. Our center protocol consisted of four 16 mg/kg IV doses spaced out weekly and used for persistent AMR especially in cases with class II donor specific anti-HLA antibodies.
Results: We observed significant decreases in anti-HLA antibodies independent of HLA gene directly following Daratumumab treatment. Figure 1 demonstrates post heart transplant, the effect of our four dose course to decrease donor specific anti-HLA antibodies. 56% of Heart Transplant patients still had persistent AMR at 1 year follow up, yet no graft losses. Non-compliant patients were more likely to still have rejection thought their anti-HLA antibodies titers had decreased. None of the recipients experienced T cell mediated rejection. Minimal side effects included itching, rash (N=1) and anaphylaxis (N=1) after first dose. The risk of infection was not significant with no neutropenia observed, yet 1 patient had an ANC <500 and 2 patients did receive GCSF.
Conclusion: Daratumumab effectivity deceased the titer of MHC class I and II donor specific anti-HLA antibodies across all eleven Heart Transplant cases. It was well tolerated and low risk of infection. Maintaining anti-HLA antibodies at low titers decreased their ability to crosslink and diminished their effector responses to cause graft failure. Daratumumab should be considered post transplant for persistence AMR with high titers of donor specific anti-HLA antibodies that do not response to other AMR treatments.
