Efficacy and safety of desensitization protocol based on rituximab and tacrolimus in living donor kidney transplantation recipients with preformed anti-HLA antibodies and/or donor-specific antibodies: an open-label, single-arm, multicenter clinical study in Japan

Abstract

【Objective and Design】 To prevent antibody-mediated rejection (ABMR) and adequately suppress the immune response following transplantation, desensitization is performed in donor-specific antibody (DSA) or anti-human leukocyte antigen antibody positive kidney transplant recipients. However, no standard desensitization method has been established. Therefore, we conducted an open-label, non-randomized, multicenter Phase III study to evaluate the efficacy of rituximab and tacrolimus in a desensitization protocol.

【Methods】 Living donor kidney transplant recipients aged 16 to 74 years who were positive for complement-dependent cytotoxicity cross-match (CDCXM), flow cytometric cross-match (FCXM), or DSA were eligible for the study. Patients received pre-transplant desensitization with rituximab, tacrolimus, mycophenolate mofetil, glucocorticoid, and plasma exchange (optional). The primary endpoint was graft survival rate at 24 weeks post-transplant, estimated using Bayesian analysis.

【Results】 Of the original 25 patients, 24 received rituximab. Baseline histocompatibility testing showed no patients to be T-CDCXM-positive. Twenty-two patients underwent kidney transplantation (91.7%, 95% confidence interval: 73.0; 99.0%). Patient and graft survival rates at 48 weeks were both 100%. ABMR developed in four patients (18.2%). In Bayesian analysis, the mode for graft survival rate at 24 weeks post-transplant was 90.8% (95% credible interval: 81.3; 95.6%), and the posterior probability below the threshold 74.9% was 0.1%. There were no serious adverse events related to desensitization that led to discontinuation of the study.

【Conclusion】 The study demonstrated that CDCXM, FCXM, and DSA-positive patients can safely undergo kidney transplantation following desensitization including rituximab and tacrolimus, and that such desensitization is effective and well tolerated for up to 48 weeks post-transplant.