A NOVEL treatment approach combining daratumumab (Dara) and tocilizumab (TCZ) offers hope for patients experiencing late antibody-mediated rejection (AMR) after kidney transplantation. This breakthrough could address a critical unmet need in managing this complex condition.
The pilot study examined seven renal transplant recipients with late or chronic active AMR marked by high or moderate levels of de novo donor-specific antibodies (DSA). Researchers implemented a two-phase treatment strategy: Phase 1 included intensive desensitisation with Dara and plasma exchange/intravenous immunoglobulin (PP/IVIG), followed by Dara maintenance therapy. Phase 2 introduced TCZ to address lingering or rebounding DSAs.
The results were encouraging. During Phase 1, DSA levels dropped below 5,000 mean fluorescence intensity (MFI) in five out of seven patients. However, only one patient achieved DSA negativity during Dara maintenance, while others experienced stable or rebounding DSAs. Phase 2 with TCZ further improved outcomes, rendering DSA levels undetectable in three patients and reducing them to low levels in the remaining three.
Renal function stabilised across all participants, and follow-up biopsies at 24–28 months showed reduced microvascular inflammation in four out of six patients, with capillary C4d deposition eliminated in all cases (P=0.001).
“This combination therapy offers a promising desensitisation effect and represents a significant step forward in addressing late AMR, a condition with limited current treatment options,” the authors wrote.
While further research is needed, this study provides a foundation for developing more effective strategies for managing late or chronic active AMR, improving outcomes for kidney transplant recipients.
Aleksandra Zurowska, EMJ
Reference
Guo Z et al. 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. BMC Nephrol. 2025;DOI: 10.1186/s12882-025-03951-5.
