013 - A global anti B cell strategy combining Obinutuzumab and Daratumumab for Treatment of Antibody-Mediated Rejection in Pediatric Kidney transplantation

Publication Number: 13.3816

Raja Dandamudi, Washington University in St. Louis School of Medicine, St.Louis, MO, United States; Hannah Foiles, St. Louis Children's Hospital, Jerseyville, IL, United States; Dawn Bunton, St. Louis Children's Hospital, St. Louis, MO, United States; Jennifer Young, St. Louis Children's Hospital, Saint Louis, MO, United States; Patricia Fredrick, St. Louis Children's Hospital, Lake St. Louis, MO, United States; Vikas Dharnidharka, Rutgers, Robert Wood Johnson Medical School, New Brunswick, NJ, United States

Background: Antibody-mediated rejection (AMR) is a leading cause of kidney transplant failure and poses unique challenges in pediatric patients, especially in cases refractory to conventional therapies such as plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab. This study focuses on biopsy proven C4d+ AMR in pediatric kidney transplant recipients who were maintained on corticosteroids, a calcineurin inhibitor, and an antimetabolite.

Objective: The authors aimed to describe their experiences using a combination of Obinutuzumab and Daratumumab to treat refractory C4d+ AMR, assessing both renal function and reduction in HLA donor-specific antibodies (DSAs).

Design/Methods: Six pediatric patients (median age 15.5 years) with refractory C4d+ AMR, unresponsive to traditional treatments, received a single intravenous dose of Daratumumab at 16 mg/kg on day 1, followed by a single dose of Obinutuzumab at 1000 mg/1.73 m² on day 14. All patients were on maintenance corticosteroids, a calcineurin inhibitor, and an antimetabolite. Renal function was evaluated through serum creatinine and donor-derived cell-free DNA (dd-cfDNA, AlloSure) before and after treatment.

Results: Initial and post-treatment measurements showed creatinine levels reduced from 2 mg/dL to 1.45 mg/dL, and AlloSure levels dropped from 1.35% to 0.28%. Additionally, reductions in HLA DSAs were more effective for Class I than Class II antibodies. The combination therapy led to significant improvements in renal function, with reductions in serum creatinine (p < 0.05) and dd-cfDNA (p < 0.01), suggesting reduced allograft injury and improved renal function. The reduction in HLA DSAs was notably more effective for Class I than for Class II antibodies, further supporting the efficacy of this approach in refractory cases.

Conclusion(s): This study suggests that sequential administration of Daratumumab and Obinutuzumab may be effective in managing refractory C4d+ AMR in pediatric kidney transplant patients, as demonstrated by improved renal biomarkers and reduction in HLA Class I DSAs. These findings warrant further investigation to confirm efficacy and optimize treatment protocols.

Pre and Post treatment trends of creatinine and Donor derived cell free DNA
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