Combined Induction Therapy with Rabbit Antithymocyte Globulin and Rituximab in Highly Sensitized Renal Recipients

Abstract

Compared to non-sensitized renal transplant recipients, patients with preformed alloantibodies are at greater risk of cellular and humoral rejection and premature graft failure. We explored the effects of adding B-cell depleting agent (rituximab) to standard rabbit anti-thymocyte globulin (rATG) induction regimen for patients with panel reactive antibody levels >50%. Following induction therapy, 14 recipients were given two doses of rituximab (375 mg/m²) within the first month post-transplantation. Their long-term outcomes were compared to a historical control group of 23 recipients who received rATG alone. Graft survival at 5 years was superior with combination therapy compared to induction therapy alone (92.9 versus 48.3%, respectively, p = 0.02). While 30% of the rATG alone group experienced cellular rejection and 26% humoral rejection, none of rituximab plus rATG renal transplant recipients group had rejection. Thus, addition of rituximab to rATG provided superior outcomes to rATG alone. This combination induction therapy should be considered for a high-risk population.

• B-cell depleting
• humoral rejection
• PRA
• thymoglobulin

Acknowledgement

The authors would like to thank Julian Ambrus Jr, MD, PhD, for his review and recommendations of this article.

Declaration of interest

This research is unfunded and the authors have no financial disclosures or conflict of interest except Mark Laftavi who received research support from Genzyme and Novartis; he has also received honoraria for being a speaker for Novartis. Oleh Pankewycz has received research support from Novartis, Genentech and Astellas.