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 H.; Kanellis, John; Pilmore, Helen; Campbell, Scott; Masterson, Rosemary; Walker, Rowan G.; O’Connell, Philip J.; Russ, Graeme; Chadban, Steven J.

doi:10.1111/ajt.14948

Cited by 18 publications

(13 citation statements)

References 36 publications

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“…Hence, mTOR inhibitor–based regimens have been used de novo to prevent cancer development in transplant patients with high cancer risk and conversion to an mTOR inhibitor–based regimen is often considered if cancer is diagnosed. Whereas a 2014 meta-analysis showed a decreased risk of malignancy by 40% (driven mainly by the decreased risk of non-melanoma skin cancer) 112 , recent large studies have failed to show a difference in overall malignancy risk between patients on mTOR inhibitor–based immunosuppression and other regimens 113– 116 . Some studies have not included non-melanoma skin cancer in their analysis, but most of the studies that did have found a decreased risk of non-melanoma skin cancer (particularly basal cell carcinoma) 112, 114, 116– 119 .…”

Section: Cancermentioning

confidence: 99%

“…Whereas a 2014 meta-analysis showed a decreased risk of malignancy by 40% (driven mainly by the decreased risk of non-melanoma skin cancer) 112 , recent large studies have failed to show a difference in overall malignancy risk between patients on mTOR inhibitor–based immunosuppression and other regimens 113– 116 . Some studies have not included non-melanoma skin cancer in their analysis, but most of the studies that did have found a decreased risk of non-melanoma skin cancer (particularly basal cell carcinoma) 112, 114, 116– 119 . Nonetheless, mTOR inhibitor–based immunosuppression regimens have been associated with increased risk of mortality 112, 115 and post-transplant lymphoproliferative disorder 120, 121 .…”

Section: Cancermentioning

confidence: 99%

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Non-immunological complications following kidney transplantation

2019

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Kidney transplantation (KT) is the most effective way to decrease the high morbidity and mortality of patients with end-stage renal disease. However, KT does not completely reverse the damage done by years of decreased kidney function and dialysis. Furthermore, new offending agents (in particular, immunosuppression) added in the post-transplant period increase the risk of complications. Cardiovascular (CV) disease, the leading cause of death in KT recipients, warrants pre-transplant screening based on risk factors. Nevertheless, the screening methods currently used have many shortcomings and a perfect screening modality does not exist. Risk factor modification in the pre- and post-transplant periods is of paramount importance to decrease the rate of CV complications post-transplant, either by lifestyle modification (for example, diet, exercise, and smoking cessation) or by pharmacological means (for example, statins, anti-hyperglycemics, and so on). Post-transplantation diabetes mellitus (PTDM) is a major contributor to mortality in this patient population. Although tacrolimus is a major contributor to PTDM development, changes in immunosuppression are limited by the higher risk of rejection with other agents. Immunosuppression has also been implicated in higher risk of malignancy; therefore, proper cancer screening is needed. Cancer immunotherapy is drastically changing the way certain types of cancer are treated in the general population; however, its use post-transplant is limited by the risk of allograft rejection. As expected, higher risk of infections is also encountered in transplant recipients. When caring for KT recipients, special attention is needed in screening methods, preventive measures, and treatment of infection with BK virus and cytomegalovirus. Hepatitis C virus infection is common in transplant candidates and in the deceased donor pool; however, newly developed direct-acting antivirals have been proven safe and effective in the pre- and post-transplant periods. The most important and recent developments on complications following KT are reviewed in this article.

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Section: Cancermentioning

confidence: 99%

Section: Cancermentioning

confidence: 99%

Non-immunological complications following kidney transplantation

2019

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“…Recently, the TRANSFORM randomized trial showed that EVR in association with reduced CNI exposure was as effective as the standard CNI‐mycophenolic acid (MPA) regimen for preventing the occurrence of dn DSA and rejection in patients with mild to moderate immunologic risk, 41 with a very good safety profile. Interestingly, the association of mTORi with a low‐dose CNI could be sufficient to reduce cancer frequency 28,42‐44 . Based on these data, we proposed to our KTRs with at least one NMSC a conversion to EVR in association with reduced CNI exposure.…”

Section: Introductionmentioning

confidence: 90%

Comparison of two strategies based on mammalian target of rapamycin inhibitors in secondary prevention of non‐melanoma skin cancer after kidney transplantation, a pilot study

Préterre

Visentin

Cricq

et al. 2021

Clinical Transplantation

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After kidney transplantation, withdrawal of calcineurin inhibitors (CNI) and conversion to sirolimus (SRL) may reduce the occurrence of new non‐melanoma skin cancer (NMSC). Conversely, a reduced CNI exposure with everolimus (EVR) is an alternative strategy that has not been thoroughly evaluated. We retrospectively compared the occurrence of newly diagnosed NMSCs in two cohorts of kidney transplant recipients (KTR) with at least one NMSC: 35 patients were converted to EVR with reduced CNI exposure (CNI/EVR group), whereas 46 patients were converted to SRL in association with mycophenolic acid (MPA) (SRL/MPA group). Two years after conversion, survival free of new NMSC was similar between the two cohorts (p = .37), with 19 KTR (54.3%) in the CNI/EVR group and 22 (47.8%) in the SRL/MPA group being diagnosed of at least one new NMSC. Half of the KTR from both groups showed adverse events, leading to mTORi discontinuation for 37.1% of KTR in the CNI/EVR group and 21.7% in the SRL/MPA group (p = .09). The incidence of rejections was similar between the two groups. In a retrospective cohort of KTR with at least one post‐transplant NMSC, the outcome of the patients converted to a CNI/EVR regimen was not different from those converted to a SRL/MPA regimen.

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“…In addition, the impact c o m m e n t a r y Kidney International (2019) 96, 13-30 on longer-term, hard outcomes will be the ultimate determinant of comparative efficacy, given associations between mTORi and increased mortality in registry studies and meta-analyses, yet some evidence that de novo mTORi may afford protection from cancer. 9 Exactly how this data will be obtained remains unclear because the 3 trials discussed were short term only. Linkage to registries 9 or administrative data sets may provide some of the answers.…”

mentioning

confidence: 99%

“…9 Exactly how this data will be obtained remains unclear because the 3 trials discussed were short term only. Linkage to registries 9 or administrative data sets may provide some of the answers. DISCLOSURE SC has received research funding (to institution), travel support, or speakers fees from Novartis, Astellas, Amgen, and Vitaeris.…”

mentioning

confidence: 99%