Risk of Malignancy with Immunosuppressive Drugs Used in Organ Transplants Compared to Those Used for Non-Transplant Indications

Authors

• Connor Haines, University of Texas Medical Branch
• Zachary Walton, University of Texas Medical Branch
• Ian Curnutt, Kansas City University
• George Golovko, University of Texas Medical Branch
• Yong-Fang Kuo, University of Texas Medical Branch
• Cristiana Rastellini, University of Texas Medical Branch
• Luca Cicalese, University of Texas Medical Branch

Document Type

Article

Publication Title

Cancers

Abstract

Background: Immunosuppressive drugs (ISDs) are essential for preventing organ rejection but have been reported to increase cancer risk with prolonged use. This study compares cancer risk between ISDs used for long-term maintenance after transplantation (T-ISDs) and those prescribed for non-transplant chronic conditions including cell-mediated (C-ISDs) and receptor-mediated (R-ISDs) ISDs. We hypothesized that cancer risk would differ between T-ISDs and both C-ISD and R-ISD groups. Methods: Using the TriNetX database, solid organ transplant recipients treated with tacrolimus (TAC), cyclosporine (CY), rapamycin (RAPA), or mycophenolate (MMF) were compared to propensity-matched R-ISDs (adalimumab, infliximab, etc.) or C-ISDs (methotrexate, azathioprine, etc.) for at least 24 encounters to determine risk of malignancy. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the three-year cancer risk. Results: After matching, T-ISDs were associated with higher malignancy risk compared to both R-ISDs (n = 29,748; HR 2.616, 95% CI 2.427-2.820) and C-ISDs (n = 31,704; HR 1.271, 95% CI 1.195-1.351). Each individual immunosuppressant in the T-ISD cohort was associated with increased cancer risk compared to R-ISDs, while only TAC and CY showed higher risk than C-ISDs (TAC: n = 9846, HR 1.354, 95% CI 1.228-1.492; CY: n = 1801, HR 1.234, 95% CI 1.007-1.512). Organ-specific analyses showed consistent patterns across systems. Conclusions: Overall, T-ISDs are associated with increased malignancy risk compared to R-ISDs and modestly compared to C-ISDs. TAC and CY confer the greatest risk, while MMF demonstrates relatively lower relative risk. These findings underscore the need to individualize ISD regimens to minimize long-term cancer risk.

DOI

10.3390/cancers18111784

Publication Date

5-29-2026

Keywords

cell-mediated, immunosuppressants, malignancy, neoplasia, non-transplant, receptor-mediated, transplant

ISSN

2072-6694

Recommended Citation

Haines C, Walton Z, Curnutt I, Golovko G, Kuo Y, Rastellini C, Cicalese L. Risk of Malignancy with Immunosuppressive Drugs Used in Organ Transplants Compared to Those Used for Non-Transplant Indications. Cancers. 2026; 18(11). doi: 10.3390/cancers18111784.