A TWO DOSE REGIMEN OF DACLIZUMAB (ZENAPAX) IN HIGH-RISK RENAL TRANSPLANT RECIPIENTS:

311 Introduction: The recommended dosing of the new humanized anti-IL-2 receptor monoclonal antibody, daclizumab (Zenapax), is 5 doses biweekly over a period of 8 weeks. After the release of Zenapax in the U.S. in January 1998, we substituted Zenapax for OKT3 induction in high-risk renal transplant patients. We opted to reduce treatment with Zenapax to two doses. Methods: Between 1/14/98 and 10/7/98, 14 high-risk recipients received induction treatment the two-dose course of Zenapax. They included sensitized (PRA≥30%) recipients (n=2), African-Americans (n=5), and those who had rejected a prior kidney transplant (n=7). Nine were cadaveric kidney recipients and 5 were living-related donor recipients. Zenapax was administered just prior to transplantation and again on post-transplant day 14. Maintenance immunosuppression, begun immediately after transplantation, consisted of cyclosporine microemulsion (Neoral), mycophenolate mofetil and corticosteroid, following our standard protocol. The end points measured were patient and graft survival, incidence of delayed graft function, incidence of acute rejection and serum creatinine at time of follow-up. Results: The length of follow-up is 2 to 10 months. There were 2 cases of primary non-function (with no evidence of rejection on allograft biopsy). There were no episodes of delayed graft function. Reversible acute rejection has occurred in 2 of the remaining 12 (2/12, 17%) recipients; both were undergoing repeat transplantation. In the 12 recipients with functioning allografts, the average of their most recent serum creatinines is 1.5 mg/dL (range 1.0-2.4 mg/dL). Patient survival is 100% and graft survival is 85.7% to date. There were no adverse effects or infectious complications. Conclusion: Induction treatment with a two-dose course of Zenapax, in combination with a maintenance immunosuppressive regimen consisting of Neoral, mycophenolate mofetil and corticosteroid, resulted in a low frequency of acute rejection in a small group of high-risk kidney transplant recipients. The acute rejection rate of 17% compares favorably with the reported acute rejection rates of 22% and 28% in the kidney transplant recipients (all first cadaveric kidney transplant recipients) receiving Zenapax in its phase III trials.