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Cumulative exposure to tacrolimus tied to post liver transplant cancer risk

American Journal of Transplantation
Reuters Health - 21/03/2022 - Higher cumulative exposure to tacrolimus in the first year after liver transplant was linked to a higher risk for de novo malignancies and recurrent liver cancer in a case-control study from Spain. 

Researchers at 16 transplant centers studied 2,945 patients who underwent liver transplantation between 2010 and 2015 and were treated with tacrolimus, including 491 (19.7%) who developed cancer during a median follow up of 65 months. Incidence rates were 3.5/100 person-years for all type of tumors and 2.6/100 persons-years for de novo cancers. 

After controlling for liver cancer, risk factors for posttransplant malignancy included age greater than 50 at transplant, male gender, active smoking, and alcoholic liver disease. Cancer risk rose with number of risk factors, reaching 24.9% at years for patients with four risk factors, Dr. Manuel Rodríguez-Perálvarez of Hospital Universitario Reina Sofía and the University of Córdoba and colleagues reported in the American Journal of Transplantation. 

To analyze immunosuppression-related risk factors, the researchers compared 425 patients who developed either recurrent liver cancer or non-liver de novo cancers to 425 matched controls who did not develop malignancy. Cumulative exposure to tacrolimus was measured by calculating the area under the curve of trough tacrolimus levels. 

The predominant immunosuppression protocols during the first 12 months posttransplant were tacrolimus alone or in combination with mycophenolate or with mTOR inhibitors, with similar rates of each protocol in the groups with and without new cancers. 

As reported in the American Journal of Transplantation, patients with posttransplant malignancy had significantly higher cumulative exposure to tacrolimus within the first three months (754 ng/day vs 695 ng/day, p=.002) and the first 12 months (2820 ng/day vs 2699 ng/day, p=0.009). 

Looking at specific cancers, an increase of cumulative tacrolimus exposure by 20% in the first 3 months was associated with significantly higher risk of de novo colorectal cancer or lung cancer and recurrent hepatocellular carcinoma. An increase by 20% in the first 12 months was associated with a higher risk of skin cancer and colorectal cancer. 

Reducing or withdrawing immunosuppression had no effect on overall survival once cancer was diagnosed. 

The authors believe that monitoring tacrolimus exposure, especially during the first three months after transplant, would help guide dose adjustments to reduce immunosuppression exposure. In patients with other identified risk factors - older age, hepatocellular cancer, active smoking and alcoholic liver disease - "a consensus is needed to delineate cancer screening strategies after liver transplant" and a "more aggressive minimization of tacrolimus" should be considered, they advise. 

SOURCE: https://bit.ly/3IxfOU6 American Journal of Transplantation, online March 14, 2022. 

By Reuters Staff 

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