Sirolimus chemoprevention supported in organ transplant recipients

By Shreeya Nanda, Senior medwireNews Reporter

In solid-organ transplant recipients (OTRs) diagnosed with cancer post-transplant, treatment with sirolimus reduces the risk of developing a subsequent skin cancer, US investigators report in JAMA Dermatology.

They reviewed the electronic medical records of 329 patients who developed cancer a median of 42 months after undergoing solid-organ transplantation. Of these, 29.5% received the mammalian target of rapamycin (mTOR) inhibitor after diagnosis of the index cancer, while the remaining 70.5% did not.

Overall, 39.5% of study participants were diagnosed with a second post-transplant malignancy, at a median of 14 months after the index cancer, with the majority (88.5%) developing skin cancer, a known risk for OTRs.

A significantly smaller proportion of sirolimus-treated patients than those not treated developed a second post-transplant cancer, at 30.9% versus 43.1%, equating to a 12.2% decrease in the risk of a subsequent cancer of any type.

This decrease was mainly driven by the reduction in subsequent skin cancer risk, with 26.8% of patients in the sirolimus group developing skin cancer compared with 38.4% in the non-treated group.

When just the 39% of patients who underwent a nonrenal transplant – previously associated with a higher rate of post-transplantation malignancy than kidney transplantation – were considered, sirolimus treatment compared with no treatment was associated with a lower incidence of a second cancer of any type and skin cancer, but the differences did not attain statistical significance.

As skin cancer was the major contributor to subsequent post-transplant cancers in the study population, the researchers conducted multivariate analysis to identify independent risk factors for skin cancer development.

Receipt of sirolimus was a protective factor against subsequent skin cancer formation (subhazard ratio [SHR]=0.6), while a history of skin cancer, either pre- or post-transplantation, significantly increased the risk (SHR=2.1 and 5.5, respectively).

The findings “highlight the necessity for dermatologists and transplant physicians to be aware of skin cancer history, coordinate regular posttransplant surveillance of skin cancers in OTRs (particularly patients with a history of skin cancer), and have close communication as skin cancers form to consider reduction in immunosuppressive therapy or conversion to an mTOR-based regimen if skin cancer formation is of concern”, say the study authors.

Noting that sirolimus treatment was not associated with an increase in either rejection or mortality rates, Chrysalyne Schmults (Brigham and Women’s Hospital, Boston, Massachusetts) and co-workers write: “Gradual conversion to a low-dose mTOR-based regimen may be considered in patients who develop multiple or high-risk skin cancers to decrease their skin cancer burden.”

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