Immunosuppressive Medications and Squamous Cell Skin Carcinoma: Nested Case-Control Study Within the Skin Cancer after Organ Transplant (SCOT) Cohort

Abstract

Organ transplant recipients (OTR) have a substantially elevated risk of squamous cell skin carcinoma (SCSC), largely attributed to immunosuppressive medications used to prevent graft rejection, although data to support the role of newer drugs on SCSC risk are sparse. We investigated the association between immunosuppressive medications and SCSC risk among cardiac and renal transplant recipients in the SCOT cohort study. Incident cases were ascertained through medical record review after self-report of skin biopsy (N=170). Controls without SCSC (N=324) were matched to cases on: gender, age, race, transplant year, hospital, donor type, organ transplanted, and time between transplant and interview. Conditional logistic regression was used to evaluate the association between specific medications and SCSC. Users of the older anti-metabolite azathioprine were more than twice as likely to develop SCSC (OR=2.69; 95%CI 1.23–5.84) compared to non-users. In contrast, the newer anti-metabolite preparations (i.e., mycophenolic acid [MPA]) were associated with lower SCSC risk (OR=0.43; 95%CI 0.27–0.66). This inverse association between MPA and SCSC persisted among OTR with no history of azathioprine use, even after adjustment for simultaneous use of the calcineurin inhibitor tacrolimus (OR=0.50; 95%CI 0.31–0.81). Our data suggest that the increased risk of SCSC historically associated with azathioprine is not seen in OTR prescribed newer regimens, including MPA and tacrolimus.

Clinical and Economic Consequences of Early Cancer After Kidney Transplantation in Contemporary Practice

“…Similarly, azathioprine has been associated with NMSC not only in the renal transplant recipients where it is used concomitantly with CNIs (4) but also when used alone for the treatment of Inflammatory bowel disease (38, 39). In accord with our findings, a recent case-control study of kidney and heart transplant recipients reported that azathioprine, but not MMF, was associated with increased risk of NMSC, and that the association was independent of CNIs (40). In the current study, we also noted a lower risk of NMSC in patients who received sirolimus-based regimens at discharge compared to a reference regimen based in tacrolimus and MMF; however, sirolimus was not associated with differences in the risk of viral-linked or other cancers.…”

Stopping immunosuppressive treatment in autoimmune hepatitis (AIH): Is it justified (and in whom and when)?

“…A recent large study of cardiac and renal transplant patients demonstrated a lower risk of squamous cell carcinoma in patients receiving mycophenolate (OR 0.45, 95% CI 0.29‐0.69) compared with those treated with azathioprine (OR 2.67 95% CI 1.23‐5.76) …”

Gynecologic cancers and solid organ transplantation

“…36 In contrast, one meta-analysis of kidney and kidney-pancreas transplant recipients demonstrated a significantly reduced risk of any malignancy with use of the mammalian target of rapamycin (mTOR) inhibitor, sirolimus (adjusted hazard ratio [aHR] 0.60, 95% CI 0.39-0.93), although this was driven by keratinocyte carcinomas as well. 3,38,39 Data on the direct effect of specific immunosuppressants on gynecologic, including oncogenic virus-related, cancers is sparse and often conflicting. 3,38,39 Data on the direct effect of specific immunosuppressants on gynecologic, including oncogenic virus-related, cancers is sparse and often conflicting.…”

“…37 Mycophenolate has also been potentially associated with lower cancer rates, perhaps because of its activity against an enzyme, inosine monophosphate dehydrogenase, that is expressed at high levels in some solid tumors. 3,38,39 Data on the direct effect of specific immunosuppressants on gynecologic, including oncogenic virus-related, cancers is sparse and often conflicting. A registry study in the United States reported variable results with different immunosuppressants.…”