A BLINDED, LONG-TERM, RANDOMIZED MULTICENTER STUDY OF MYCOPHENOLATE MOFETIL IN CADAVERIC RENAL-TRANSPLANTATION - RESULTS AT 3 YEARS

Background. Three large-scale clinical trials conducted in North Ameri ca, Europe, and Australia showed that mycophenolate mofetil (MMF) decr eases the incidence of acute renal allograft rejection in the first 6 months after transplant compared with placebo or azathioprine. This st udy extends the randomized, prospective, double-blind trial of MMF con ducted by the Tricontinental Mycophenolate Mofetil Renal Transplantati on Study Group. Methods. Patients (n=503) were randomized to receive 1 00-150 mg of azathioprine (AZA) (n=166), 2 g of MMF (n=173), or 3 g of MMF (n=164) per day, in conjunction with cyclosporine and prednisone from the time of transplantation. Results. During the first 6 months, the incidence of biopsy-proven acute graft rejection (BPR) was reduced by similar to 50% in the MMF 2 g (19.7%) and MMF 3 g (15.9%) groups c ompared with the AZA group (35.5%). The incidence of treatment failure during the first 6 months, including BPR, death, graft loss, and earl y withdrawal without prior EPR, was significantly decreased: AZA, 50%, compared with MMF 2 g, 38.2% (P=0.0287), and MRIF 3 g, 34.8% (P=0.004 5). At 3 years after transplant, both intent-to-treat and on-study (ce nsoring at 90 days after treatment) analyses of graft and patient surv ival showed a trend toward advantage for MMF 2 g and 3 g vs, AZA (inte nt-to-treat: 81.9% and 84.8% vs. 80.2%; on-study: 84.0% and 86.4% vs. 82.7%), although this trend did not reach statistical significance, Re jection was the principal cause of graft loss in all groups: AZA, 9.9% ; MMF 2 g, 5.8%; and MMF 3 g, 3.0%. Graft function (intent-to-treat an d on-study) was comparable in all three groups at 3 years, Gastrointes tinal toxicity, leukopenia, and tissue-invasive cytomegalovirus diseas e were more common in the MMF 3 g group both during and after the firs t posttransplant year. Lymphoproliferative disorders were diagnosed in one AZA (0.6%), two MMF 2 g (1.2%), and three MMF 3 g (1.8%) patients . Other (non-lymphoproliferative disorders, noncutaneous) malignancies occurred in six AZA (3.7%), four MMF 2 g (2.3%), and nine MMF 3 g (5. 5%) patients. Mortality was comparable in all three groups (AZA, 8.6%; MMF 2 g, 4.7%; MMF 3 g, 9.1%) by 3 years of follow-up. Conclusion. MM F significantly reduced the incidence of rejection in the first 6 mont hs, but there was not a significant improvement in graft survival thro ughout the 3 years after cadaver kidney transplantation.