*Purpose: Adult kidney-transplant (KT) recipients have a differential risk of malignancies based on their induction immunosuppression (IS) therapy. However, older recipients are more likely to experience immunosenescense and therefore, may have a different risk of malignancy than younger recipients. We compared the risk of incident malignancy among younger (18-64) and older (≥65) KT recipients by use of the two most common induction IS agents: anti-thymocyte globulin (ATG, rATG and eATG) and interleukin-2 receptor antagonist (IL-2 RA, basiliximab and daclizumab).

*Methods: A total of 66,700 adult (age≥ 18) first-time KT recipients were identified using either ATG (n=40,443) or IL2-RA (n=26,327) between January 1, 1999 and December 31, 2014 with the United States Renal Data System linked to Medicare claims. Kaplan-Meier estimator was used to generate the cumulative incidence of first-diagnosed malignancy after KT. The Cox proportional hazard model was used to estimate hazard ratios (HR) of any and specific incident malignancy comparing ATG to IL-2 RA. All models incorporated weighting with inverse propensity score to adjust for confounders. Propensity scores for each individual was generated as the average of estimated probabilities from logistic regression models among multiple imputation datasets for missing values in putative confounders.

*Results: The 6-month, 1-year and 3-year cumulative incidences of any malignancy were 2.32%, 4.46% and 11.95% respectively. In overall, the use of ATG induction was associated with higher risk of post KT malignancy (HR 1.11, 95% CI 1.05-1.17, p<0.001) compared with IL-2 RA induction. This effect of IS on incident malignancy was similar among younger recipients (HR 1.12, 95% CI 1.06-1.18, p<0.001) and older recipients (HR 1.07, 95% CI 1.01-1.14, p<0.05; interaction p=0.392). For specific malignancy, ATG induction is associated with higher risk of post KT skin malignancy (HR 1.22, 95% CI 1.12-1.33, p<0.001), while there was no significant evidence suggesting that ATG induction is associated with higher risk of kidney malignancy (HR 1.03, 95% CI 0.89-1.18, p=0.684) or lymphoma malignancy (HR 1.12, 95% CI 0.99-1.27, p=0.064).

*Conclusions: Compared with IL-2 RA induction, ATG induction is associated with elevated risk of post-transplant malignancy; these effects did not differ by age. Transplant centers do not need to tailor induction IS by age to mitigate malignancy risk.

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