CHICAGO – Compared with that of calcineurin inhibitors, belatacept appears to be associated with a lower risk of keratinocyte carcinomas in solid organ transplant patients, based on results from a single-center analysis presented at the annual meeting of the Society for Investigative Dermatology.
“Belatacept may offer a better risk-benefit profile in regards to skin cancer,” reported Michael Wang, a medical student who conducted this research in collaboration with the senior author,, PhD, an associate professor of dermatology, pathology, and surgery at Yale University, New Haven, Conn.
Belatacept, a CTLA-4 fusion protein, has been compared with calcineurin inhibitors in two previous studies. The results were equivocal in one, and the other found no difference in risk and could not rule out the possibility that skin cancer risk was even higher on belatacept.
This single-center chart review included 110 kidney transplant patients, median age 58 years, who were switched from a calcineurin inhibitor, such as cyclosporine or tacrolimus, to belatacept. Ultimately, the study was limited to the 66 patients with at least 2 years of dermatologic follow-up both before and after the switch from a calcineurin inhibitor.
The primary outcome was the number of keratinocyte carcinomas overall and, specifically, the number of squamous cell carcinomas (SCCs) before and after the switch. Over the course of this study there were 128 cutaneous malignancies, 83 of which were SCCs.
When patients were on a calcineurin inhibitor, the risk of keratinocyte carcinomas increased incrementally by 2.6 events per 100 patients per year of follow-up, and the risk of SCCs increased by 1.7 events per 100 patients per year of follow-up. In the first 6 months after the switch to belatacept, there was no change in the rising trajectory of skin cancers, but rates declined thereafter.
Relative to rates prior to and 6 months after the switch, “the incidence of SCCs decreased at a rate of 5.9 events per 100 patients per year (P = .0068), and the incidence of keratinocyte carcinomas decreased by 7.1 events per 100 patients per year (P = .003),” Mr. Wang reported. He noted, however, that the incidence of basal cell carcinomas and melanomas following the switch remained unchanged.
When patients switched to belatacept were compared with another group of patients who remained on a calcineurin inhibitor after developing a SCC, the hazard ratio for a new SCC was 0.42, indicating a greater than 50% reduction in risk.
In patients on calcineurin inhibitors, the risk of keratinocyte carcinomas appears to be related to a direct effect of these agents on keratinocyte dedifferentiation. Belatacept is not believed to have any direct effects on keratinocytes, according to Mr. Wang.
As the chart review was retrospective and limited to a single center, “we hope [the findings] will encourage a prospective trial,” Mr. Wang said.
SOURCE: Wang M. SID 2019, .