Management of Immunosuppression in Kidney Transplant Recipients Who Develop Malignancy

Abstract

The risk of cancer increases after transplantation. However, the consensus on immunosuppression (IS) adjustment after diagnosis of malignancy is lacking. Our study aims to assess the impact of IS adjustment on mortality of post-kidney transplant patients and allograft outcomes. We retrospectively reviewed the data in our center of 110 subjects. Our results showed IS dose adjustment was not statistically associated with mortality risk (HR 1.94, 95%CI 0.85–4.41, p = 0.12), and chemotherapy was the only factor that was significantly related to mortality (HR 2.3, 95%CI 1.21–4.35, p = 0.01). IS reduction was not statistically associated with worsening graft function (OR 3.8, 95%CI 0.77–18.71, p = 0.10), nor with graft survival (SHR 4.46, 95%CI 0.58–34.48, p = 0.15) after variables adjustment. Creatinine at cancer diagnosis and history of rejection were both negatively associated with graft survival (SHR 1.72, 95%CI 1.28–2.30, p < 0.01 and SHR 3.44, 95%CI 1.25–9.49, p = 0.02). Reduction of both mycophenolate and calcineurin inhibitors was associated with worsening graft function and lower graft survival in subgroup analysis (OR 6.14, 95%CI 1.14–33.15, p = 0.04; HR 17.97, 95%CI 1.81–178.78, p = 0.01). In summary, cancer causes high mortality and morbidity in kidney transplant recipients; the importance of cancer screening should be emphasized.

Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients

“…In these scenarios, 58% to 67%, depending on the specific query, of the panel preferred to defer this decision to transplant physicians. Although the absence of such a recommendation runs contrary to previous expert statements and some RCTs have demonstrated that reduction of immunosuppression or conversion to mTOR-based immunosuppression may decrease CSCC formation, this discrepancy is instructive regarding the balance expert physicians must use in management of SOTRs: patients with reduced immunosuppression are at risk for inferior graft survival, and conversion to mTOR may affect overall survival …”

Managing immunosuppressive therapy in potentially cured post‐kidney transplant cancer (excluding non‐melanoma skin cancer): an overview of the available evidence and guidance for shared decision‐making

“…There are no systematic reviews or RCTs on this topic. Only two small ( n = 87 and n = 110), retrospective cohort studies were identified [ 7 , 8 ] comparing outcomes in KTRs with post‐transplant cancer between those remaining on standard immunosuppression and those who underwent reduction of immunosuppression. However, no clear conclusions could be drawn from these studies because of the low number of patients, high heterogeneity of cancer types and cancer stages, varying immunosuppressive regimens and a high risk of indication bias, because the patients who were switched to a reduced immunosuppressive regimen are more likely to be those with an inferior prognosis (Table S1 ).…”

“…There are no systematic reviews or RCTs on this topic. Only two small (n = 87 and n = 110), retrospective cohort studies were identified [7,8] who were switched to a reduced immunosuppressive regimen are more likely to be those with an inferior prognosis (Table S1). A second literature search, specifically on PTLD, yielded no studies matching our inclusion criteria (Fig.…”

Local blockade of tacrolimus promotes T-cell-mediated tumor regression in systemically immunosuppressed hosts

“…However, no strategies have proven effective without unacceptable impacts on transplanted organs and/or the patients themselves. For example, reducing the dose of immunosuppressive medications can decrease malignancy rates, however, such approaches have been linked to an increased risk of graft failure 16 and an increased frequency of transplant rejection. 17 Alternatively, switching from a calcineurin inhibitor-based treatment regime to a mammalian target of rapamycin (mTOR) inhibitor-based treatment regimen can reduce de novo SCC formation [18][19][20][21] and induce the regression of pre-existing premalignant lesions.…”