Cumulative exposure to tacrolimus is associated with increased risk of malignancy for solid organ transplant recipients
Menée à partir de données administratives canadiennes liées aux soins de santé portant sur 5 178 receveurs de greffe d'organe solide sur la période 2008-2020, cette étude analyse l'association entre les concentrations minimales cumulées de tacrolimus et l'incidence des tumeurs malignes de novo après la greffe
Solid organ transplant recipients (SOTR) face elevated cancer risk due to prolonged immunosuppression. While higher tacrolimus exposure has been linked to de novo malignancies, the dose–response relationship remains unclear, prompting the need for population-level, longitudinal investigations. To quantify the exposure-response relationship between tacrolimus trough level and post-transplant malignancy risk, we used a population-based cohort study using linked administrative healthcare data from Ontario, Canada. All transplant recipients from January 1, 2008 to March 1, 2020 with ≥2 serum tacrolimus levels in the first year post-transplant were included. Cumulative exposure to tacrolimus was treated as a (1) continuous variable, (2) by quartiles of exposure within the first year and (3) as time-varying exposure beyond the first year; incidence of de novo malignancy was investigated using cause-specific and subdistribution Cox regression models. Among the 5178 SOTRs, a total of 318 de novo malignancies (6.1%) and 332 deaths (6.4%) occurred. For every 20% increase in the cumulative tacrolimus trough level in the first year, a heightened risk of malignancy was observed (HR = 1.09, 95% CI: 1.02–1.17). For each 20% increase in cumulative tacrolimus trough level after 1 year, the risk of malignancy increased (HR = 1.08 [95% CI: 1.01–1.15]). Patients in the highest quartile of cumulative exposure (median 9–10 ng/mL) had a 47% greater risk of malignancy compared to those in the lowest quartile (median 5–6 ng/mL; HR = 1.47 [95% CI: 1.03–2.11]). These findings highlight the importance of carefully titrating tacrolimus and avoiding unnecessary prolonged high exposure, particularly during the critical first year post-transplant.
International Journal of Cancer , article en libre accès, 2026