Daratumumab followed by tocilizumab for treatment of late antibody-mediated rejection in renal transplant recipients with high or moderate levels of de novo donor-specific antibodies: a pilot study

Effective treatment of late antibody-mediated rejection (late AMR) is still an unmet medical need. Clearing donor-specific antibody (DSA) and preventing its rebound is the ideal goal of treatment. We have summarized the clinical data from seven patients with late or chronic active AMR after renal transplantation who received daratumumab (Dara)-based treatment first (Phase 1) and then tocilizumab (TCZ) therapy (Phase 2). Phase 1 consisted of an intensive treatment period (Dara plus PP/IVIG) and a maintenance treatment period (Dara alone). The main clinical indicators were DSA, Banff scores and renal function. After 4 to 17 weeks of intensive treatment, the MFI values of DSA in five of the seven patients fell below 5,000. During Dara maintenance treatment, only one patient's DSA became negative, and the remaining six patients' DSAs remained relatively stable or showed rebound. However, after TCZ treatment was begun, the DSA eventually became negative in three patients and decreased to low levels (< 3,500) in the other three patients. Also, our treatment stabilized renal function in all patients. At 24–28 months after treatment, renal biopsy showed partial remission of microvascular inflammation in four of six patients. In addition, capillary C4d deposition became negative in all patients (P = 0.001), and the mean score of i-IFTA was significantly reduced (P = 0.012). Other chronic injury scores did not change significantly. This new therapy combining Dara and TCZ achieved a good desensitization effect, providing an important reference point for designing better-optimized treatment of late or chronic active AMR in the future. This retrospectively study was approved by the Ethics Committee of Tongji Hospital, Wuhan, China (TJ-IRB20230729).