De novo or early conversion to everolimus and long-term cancer outcomes in kidney transplant recipients

A trial-based linkage study

Tracey Ying, Germaine Wong, Wai Lim, John Kanellis, Helen Pilmore, Scott Campbell, Rosemary Masterson, Rowan Walker, Philip O'Connell, Graeme Russ, Steven Chadban

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Choice of immunosuppression may modify the risk of cancer after kidney transplantation, however, long-term data are lacking. Using the Australian and New Zealand Dialysis and Transplant Registry, we compared the 9-year risk of incident cancer, non-melanoma skin cancer (NMSC), and death attributed to cancer among participants from Australia and New Zealand in four randomized-controlled trials which compared de novo or early switch to an everolimus-containing regimen with calcineurin-inhibitor-based triple therapy. An adjusted Cox-model with random effects was used to determine such risks. Two hundred seventy-nine patients (192 everolimus, 87 control) were followed for a median of 9 years (IQR 6.7, 11.2). Compared with control, everolimus use was not associated with a reduction in the risk of incident cancer, NMSC, or cancer-related death (unadjusted HR [95% CI] 0.86 [0.49-1.48], 0.58 [0.30-1.12], and 1.18 [0.32-4.38], respectively). Subgroup analyses showed a 56% reduction for NMSC in patients randomized to everolimus + reduced-dose calcineurin-inhibitor versus control (unadjusted HR 0.44 [0.21-0.92]), which remained significant after adjusting for age, gender and smoking (adjusted HR 0.45 [0.21-0.96]). Although de novo or early switch to everolimus did not alter the 9-year risk of incident cancer or cancer-related death, everolimus with reduced-dose calcineurin-inhibitor strategy may reduce the long-term risk of NMSC.

Original languageEnglish
Pages (from-to)2977-2986
Number of pages10
JournalAmerican Journal of Transplantation
Volume18
Issue number12
DOIs
Publication statusPublished - 1 Dec 2018

Keywords

  • cancer/malignancy/neoplasia: registry/incidence
  • clinical research/practice
  • immunosuppressant - calcineurin inhibitor (CNI)
  • immunosuppressant - mechanistic target of rapamycin: everolimus
  • kidney transplantation/nephrology

Cite this

Ying, Tracey ; Wong, Germaine ; Lim, Wai ; Kanellis, John ; Pilmore, Helen ; Campbell, Scott ; Masterson, Rosemary ; Walker, Rowan ; O'Connell, Philip ; Russ, Graeme ; Chadban, Steven. / De novo or early conversion to everolimus and long-term cancer outcomes in kidney transplant recipients : A trial-based linkage study. In: American Journal of Transplantation. 2018 ; Vol. 18, No. 12. pp. 2977-2986.
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title = "De novo or early conversion to everolimus and long-term cancer outcomes in kidney transplant recipients: A trial-based linkage study",
abstract = "Choice of immunosuppression may modify the risk of cancer after kidney transplantation, however, long-term data are lacking. Using the Australian and New Zealand Dialysis and Transplant Registry, we compared the 9-year risk of incident cancer, non-melanoma skin cancer (NMSC), and death attributed to cancer among participants from Australia and New Zealand in four randomized-controlled trials which compared de novo or early switch to an everolimus-containing regimen with calcineurin-inhibitor-based triple therapy. An adjusted Cox-model with random effects was used to determine such risks. Two hundred seventy-nine patients (192 everolimus, 87 control) were followed for a median of 9 years (IQR 6.7, 11.2). Compared with control, everolimus use was not associated with a reduction in the risk of incident cancer, NMSC, or cancer-related death (unadjusted HR [95{\%} CI] 0.86 [0.49-1.48], 0.58 [0.30-1.12], and 1.18 [0.32-4.38], respectively). Subgroup analyses showed a 56{\%} reduction for NMSC in patients randomized to everolimus + reduced-dose calcineurin-inhibitor versus control (unadjusted HR 0.44 [0.21-0.92]), which remained significant after adjusting for age, gender and smoking (adjusted HR 0.45 [0.21-0.96]). Although de novo or early switch to everolimus did not alter the 9-year risk of incident cancer or cancer-related death, everolimus with reduced-dose calcineurin-inhibitor strategy may reduce the long-term risk of NMSC.",
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De novo or early conversion to everolimus and long-term cancer outcomes in kidney transplant recipients : A trial-based linkage study. / Ying, Tracey; Wong, Germaine; Lim, Wai; Kanellis, John; Pilmore, Helen; Campbell, Scott; Masterson, Rosemary; Walker, Rowan; O'Connell, Philip; Russ, Graeme; Chadban, Steven.

In: American Journal of Transplantation, Vol. 18, No. 12, 01.12.2018, p. 2977-2986.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Pilmore, Helen

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AU - Russ, Graeme

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