Immunosuppression Withdrawal in Living-donor Renal Transplant Recipients Following Induction with Anti-thymocyte Globulin and Rituximab: Results of a Prospective Clinical Trial

Durable tolerance in kidney transplant recipients remains an important but elusive goal. We hypothesized that adding B cell depletion to T cell depletion would generate an immune milieu post-reconstitution dominated by immature transitional B cells, favoring tolerance. The Immune Tolerance Network ITN039ST RESTARRT was a prospective multicenter pilot study of live donor kidney transplant recipients who received induction with rabbit anti-thymocyte globulin and rituximab, and initiated immunosuppression withdrawal (ISW) at 26 weeks. The primary endpoint was freedom from rejection at 52 weeks post-ISW. Six of ten subjects successfully completed ISW. Of these six subjects, four restarted immunosuppression due to acute rejection or recurrent disease, one remains immunosuppression-free for over 9 years, and one was lost to follow-up after being immunosuppression-free for 42 weeks. There were no cases of patient or graft loss. CD19+ B cell frequencies returned to pre-depletion levels by 26 weeks post-transplant; IgD+CD27- naïve B cells predominated. In contrast, memory cells dominated repopulation of the T cell compartment. A regimen of combined B and T cell depletion did not generate the tolerogenic B cell profile observed in preclinical studies and did not lead to durable tolerance in a majority of kidney transplant recipients. NCT01318915