532 Switching from calcineurin inhibitors to belatacept decreases keratinocyte carcinomas incidence rate in kidney transplant recipients

Abstract

Immunosuppressive calcineurin inhibitors (CNI) have been shown to increase the rates of skin cancers in solid organ transplant recipients (SOTR). Belatacept, a CTLA-4 fusion protein, is an immunosuppressant that is also used in SOTR populations. However, how belatacept affects skin cancer risk is not well characterized; the existing data compared to CNI are equivocal. We investigated the rate of skin cancer development in a retrospective study of 110 kidney transplant recipients who switched from CNI to belatacept. Of these patients, 66 were included for final analysis as they were followed by dermatology for at least 2 years after switching to belatacept. 24 patients developed a total of 128 cutaneous malignancies (38 basal cell carcinomas [BCC], 83 SCC, and 7 melanomas or atypical melanocytic proliferations). The rate of developing keratinocyte carcinomas (KC), in particular cutaneous squamous cell carcinomas (SCC) decreased after switching to belatacept. While on CNI, the incidence of developing a cutaneous KC or SCC increased by 2.6 events per 100 patients per year and 1.7 events per 100 patients per year, respectively. The incidence continued to increase to a maximum at 6 months after switching to belatacept. Thereafter, the incidence of developing cutaneous KCs or SCCs decreased at a rate of 5.9 events per 100 patients per year for SCCs and 7.1 events per 100 patients per year for KCs. The differences in rates prior to and post switch to belatacept were statistically significant: p¼0.0030 and p¼0.0068 for KCs and SCCs respectively. BCC and melanocytic lesion incidence rates were unchanged. Unlike CNI, belatacept has not been shown to have direct effects on cutaneous carcinogenesis. Belatacept has previously been shown to have better patient and graft survival compared to CNI. Our results demonstrate that it may also offer SOTR a better risk-benefit profile with regards to skin cancer. Background: A significant proportion of advanced basal cell carcinomas (BCCs) are incompletely treated with current therapies. As BCCs have particularly high mutational burdens and can express Programmed Death ligand (PDL)-1, we performed a proof-of-concept study of the PD-1 inhibitor, pembrolizumab, for advanced BCCs. Objectives: To assess the clinical effects of pembrolizumab on advanced BCCs. Methods: In this single-institution, two-cohort, nonrandomized study (NCT02690948), responses and adverse events (AEs) were assessed in patients who received 1 dose of pembrolizumab (200 mg every 3 weeks), with or without vismodegib (150mg daily). Findings: Sixteen eligible patients were enrolled and were evaluable. Overall response rate (ORR) was 38% (6/16) [95% confidence interval (CI): 15-65%], p¼0.003, at 18 weeks. ORR for pembrolizumab monotherapy group was 44% (4/9) [95% CI: 14-79%], p¼0.008 and pembrolizumab plus vismodegib group was 29% (2/7) [95% CI: 4-71%], p¼0.15. Three patients (2 with partial response and 1 with stable disease) continued to receive off-label treatment through their community oncologists and achieved comple...