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Immunosuppressant Drug Specific Risk of Malignancy After Organ Transplantation: A Population-Based Analysis of Texas Medicare Beneficiaries
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Division of Transplant Surgery, Department of Surgery, University of Texas Medical Branch, 6.120 John Sealy Annex, 301 University Boulevard, Galveston, TX 77555, USA
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Department of Biostatistics & Data Science, University of Texas Medical Branch, Galveston, TX 77555, USA
3
John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA
4
Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX 77554, USA
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(13), 2161; https://doi.org/10.3390/cancers17132161
Submission received: 15 April 2025
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Revised: 11 June 2025
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Accepted: 19 June 2025
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Published: 26 June 2025
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
Simple Summary
Though it has commonly been accepted that chronic IMD use increases the risk of cancer, the subject is largely understudied as we do not know cancer risk safety profiles for individual IMDs or individual cancer types. We analyzed the risk of cancer for the IMDs commonly used in transplant patients (tacrolimus, cyclosporin, sirolimus, mycophenolate, and their combinations) in Texas Medicare beneficiaries and from the Texas Cancer Registry between 2007 and 2018. The results of this study are vital for understanding long-term adverse effects of cancer with IMD use and highlight the importance of individualizing treatment regimens to minimize cancer risk using medications with lower risk of long-term harm. For example, TAC is one of the most commonly used IMDs in transplant but may confer the highest risk of cancer compared to other transplant IMDs according to this study.
Abstract
Background/Objectives: Prolonged use of immunosuppressive drugs (IMDs) is correlated with increased risk of cancer in transplant patients. However, detailed side-by-side analysis of cancer risk associated with individual IMDs in the same population is not available. The aim of this study was to identify drug-specific risks of cancer for commonly used transplant IMDs. Methods: We analyzed the risk of cancer for the IMDs commonly used in transplant patients (tacrolimus (TAC), cyclosporin (CY), sirolimus (SIR), mycophenolate (MMF), and their combinations) in Texas Medicare beneficiaries between 2007 and 2018. Results: Of 7721 transplant recipients receiving an IMD of interest, 2261 developed cancer. There was an increased risk of any cancer diagnosis with the use of TAC (HR: 1.49; 95% CI: 1.25–1.78) and CY (HR: 1.51; 95% CI: 1.19–1.92), and decreased risk with use of MMF (HR: 0.77; 95% CI: 0.67–0.89). Cancer-specific models revealed increased risk of liver cancer (HR: 5.25, 95% CI: 2.03–13.61) and decreased risk of ovarian/uterine cancer (HR: 0.25, 95% CI: 0.07–0.84) with TAC; increased risk of lung cancer with CY (HR: 5.06, 95% CI: 1.47- 17.41); and increased risk of lymphoma associated with SIR (HR: 2.80, 95% CI: 1.00–7.81). Conclusions: TAC increases cancer risk, and MMF decreases cancer risk. Individual cancer types also vary in risk associated with individual IMDs. This study provides new information on IMD-specific cancer risk that can guide individualized screening/treatment decisions to reduce the risk associated with specific cancers after transplantation.
