Randomized Controlled Pilot Study of B Cell–Targeted Induction Therapy in HLA Sensitized Kidney Transplant Recipients

Abstract

Optimal induction regimens for patients at high risk for antibody and/or cell-mediated rejection have not been established. This pilot, prospective, randomized study evaluated addition of B cell/plasma cell-targeting agents to T cell-based induction with rabbit antithymocyte globulin (rATG) in high immunologic risk renal transplant recipients. Patients were randomized to induction with rATG, rATG þ rituximab, rATG þ bortezomib or rATG þ rituximab þ bortezomib. Inclusion criteria were: (1) current cytotoxic panel reactive antibody (PRA) !20% or peak cytotoxic PRA !50% or (2) T or B cell positive flow crossmatch with donorspecific antibody (DSA) or (3) historical positive serologic or cytotoxic crossmatch or DSA to donor or (4) prior allograft loss with more than one acute rejection. Median overall follow-up was 496 days: 1-year and overall acute rejection were 25% and 27.5%, and 25% of patients developed de novo DSA within 1 year. One-year and overall patient survival were 97.5% and 92.5%, and 1-year and overall death-censored allograft survival were 97.5% and 95%. Renal allograft function posttransplant was similar among all arms. Eight of nine cases of peripheral neuropathy were mild, whereas one case was moderate and required a narcotic prescription. In conclusion, addition of rituximab and/or bortezomib to rATG induction has an acceptable safety/toxicity profile in a high immunologic risk renal transplant population.

A Comparison of Two Types of Rabbit Antithymocyte Globulin Induction Therapy in Immunological High-Risk Kidney Recipients: A Prospective Randomized Control Study

“…Ejaz et al showed that ATGs are the backbone of induction treatment in HLA sensitized kidney transplant recipients as even the addition of the B cell targeting agents rituximab and bortezomib alone or in combination had no influence on the overall allograft rejection episodes in these patients compared to ATG alone [23]. These data supporting several observations that ATGs have not only a T-cell depletion effect but as well a strong effect on B-cells [24;25].…”

Acute rejection in vascularized composite allotransplantation

“…A combination of total plasma exchange (TPE) and intravenous immunoglobulin (IVIG) is an effective desensitization regimen in SOT with good long-term outcomes in kidney transplantation [33][34][35]. In addition, novel B-cell targeting agents, such as Rituximab or Bortezomib, and complement inhibitors have improved the management of theses patients [36][37][38]. Five-year patient and graft survival in a group of highly sensitized recipients of kidney transplants reached 86 and 72%, respectively, with the use of a combination of agents, such as TPE, IVIG and Rituximab [35].…”

Long‐term results of desensitization protocol with and without rituximab in sensitized kidney transplant recipients

“…Two other studies reported a much lower 5-year death-censored graft survival rates of 70% 2,20. 3,10,12 Delayed appearance of de novo DSA after rituximab was reported by Ejaz et al,13 but not by others 3,10. The level of DSA decreased after desensitization in all recipients, irrespective of treatment group.…”

“…Direct comparisons with outcomes in other studies are complicated as there are inconsistencies in the definitions of sensitization, desensitization protocols, and donors'origin. Other studies only reported short-term outcome 5,12,13. Other studies only reported short-term outcome 5,12,13.…”