Everolimus Plus Reduced-Exposure Cyclosporin versus Mycophenolic Acid Plus Cyclosporin: Seven-Year Follow-Up of Australia and New Zealand Kidney Transplant Recipients in the A2309 Study.
1Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia
2Auckland Renal Transplant, Auckland City Hospital, Auckland, New Zealand
3Central Northern Adelaide Ranel and Transplantation Service, Royal Adelaide Hospital, Adelaide, Australia
4Renal Medicine, Monash Medical Centre, Melbourne, Australia
5University of Queensland, Princess Alexandra Hospital, Queensland, Australia
6Renal Medicine, Westmead Hospital, Sydney, Australia
7WA Liver and Kidney Transplant Service, Sir Charles Gairdner Hospital, Perth, Australia
8Novartis Pharmaceuticals, Sydney, Australia
9Renal Medicine, Alfred Hospital, Melbourne, Australia.
Meeting: 2016 American Transplant Congress
Abstract number: 287
Keywords: Graft survival, Immunosuppression, Kidney transplantation, Malignancy
Session Information
Date: Monday, June 13, 2016
Session Name: Concurrent Session: Belatacept and Steroid Withdrawal in Kidney Transplantation
Session Time: 4:30pm-6:00pm
Presentation Time: 5:18pm-5:30pm
Location: Ballroom A
A2309 was a 2-year, phase III randomized controlled trial evaluating the effect on graft and patient outcomes of three groups:1.5mg everolimus plus low exposure cyclosporine (EVR1.5), 3.0mg everolimus plus low exposure cyclosporine (EVR3.0) or 1.44g mycophenolic acid plus standard cyclosporine (MPA).
7-year data for 95 ANZ A2309 participants were extracted from the ANZDATA registry. Associations between treatment and outcomes, including rejection, eGFR, graft loss, death and cancer incidence were examined using adjusted generalized linear regression or Cox regression analyses by ITT analysis. Adverse events and discontinuation of study drugs (up to 2-years) were compared between treatment groups using data from Novartis.
Randomized to EVR1.5 or EVR3.0 were 66 (75.2%) recipients and to MPA 29 (24.8%. Compared to MPA, everolimus treatment was associated with adjusted hazards of 0.34 (95%CI 0.13, 0.91), 0.35 (0.09, 1.25) and 0.32 (0.15, 0.71) for non-melanoma skin cancers (NMSC), non-skin cancers and any cancers respectively, independent of age and waiting time. There was no association between treatment groups and graft function, rejection, graft loss or death up to 7-years after transplant. The adjusted mean (95%) difference in eGFR at 2 and 5-years were numerically (but not statistically significant) higher in the EVR1.5 group compared to MPA group (2 years: 8.66, 95%CI 1.46, 15.85; and 5 years: 4.68, 95%CI -5.37, 14.7mL/min/1.73m2). Adverse events and discontinuation rates were similar between treatment groups.
Compared to MPA, treatment with EVR was associated with > 50% reduction in cancer incidence, particularly NMSC. This data supports a class-effect for mTORi in reducing the burden of cancer after transplantation.
CITATION INFORMATION: Chadban S, Pilmore H, Russ G, Kanellis J, Campbell S, O'Connell P, Lim W, Lutherborrow M, Kurstjens N, Walker R. Everolimus Plus Reduced-Exposure Cyclosporin versus Mycophenolic Acid Plus Cyclosporin: Seven-Year Follow-Up of Australia and New Zealand Kidney Transplant Recipients in the A2309 Study. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Chadban S, Pilmore H, Russ G, Kanellis J, Campbell S, O'Connell P, Lim W, Lutherborrow M, Kurstjens N, Walker R. Everolimus Plus Reduced-Exposure Cyclosporin versus Mycophenolic Acid Plus Cyclosporin: Seven-Year Follow-Up of Australia and New Zealand Kidney Transplant Recipients in the A2309 Study. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/everolimus-plus-reduced-exposure-cyclosporin-versus-mycophenolic-acid-plus-cyclosporin-seven-year-follow-up-of-australia-and-new-zealand-kidney-transplant-recipients-in-the-a2309-study/. Accessed March 3, 2021.« Back to 2016 American Transplant Congress