1. There was no kidney rejection noted in the cemiplimab for kidney transplant recipients.

2. Cemiplimab was found to have a median progression-free survival and overall survival of 22.5 months.

Evidence Rating Level: 2 (Good)

Study Rundown: Solid organ transplant recipients receiving chronic immunosuppression have an increased risk of cutaneous squamous cell carcinoma (CSCC). Cemiplimab, a PD-1 inhibitor, has shown promising results in treating advanced CSCC but hasn’t been studied in transplant recipients due to concerns about organ rejection. This study investigated cemiplimab in kidney transplant recipients with advanced CSCC. The primary endpoint was safety and rate of kidney allograft rejection and secondary endpoints included objective response rate (ORR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS). An exploratory analysis was also done for PD-L1 expression and tumor mutation burden (TMB). Most common adverse events include skin disorders (83%) and fatigue (65%). Grade 3, 4, and 5 adverse events were observed in 83%, 0%, and 25% respectively. 5 deaths occurred, two from disease progression, two from unrelated medical conditions, and one from interaction between mTOR inhabitation and an ACEi. There were no kidney allograft rejection events. ORR was seen in 46% with three patients having a complete response and two having a partial response. Median DoR was 11.4 months. Median PFS was 22.5 months, median OS was 22.5 months, and the 3-month OS estimate was 72%. The median PD-L1 tumor proportion score was 1. TMB values ranged from 10 to 97, with a median of 40, and it was found that median TMB values were higher among responders (p=.05). The strengths of this study included its exploratory analysis and the limitations include the small sample size. Overall it was found that in patients with CSCC who had previous kidney transplants, cemiplimab had some response with no kidney rejection observed.

Click to read the study in JCO

Relevant Reading: mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

In-Depth [prospective cohort]: This phase I, single-arm, nonrandomized trial enrolled 12 adults with advanced CSCC who had a history of kidney transplant and switched their existing immunosuppressive regimen to an mTOR inhibitor and started them on cemiplimab for up to 35 doses (2 years) along with pulse steroids with each cycle. Initially, there was another arm of this study which included allogenic stem-cell transplant patients, but that arm was closed due to slow accrual. Median follow-up was 6.8 months. Most common adverse events include skin disorders (83%) and fatigue (65%). Grade 3, 4, and 5 adverse events were observed in 83%, 0%, and 25% respectively. 5 deaths occurred, two from disease progression, two from unrelated medical conditions, and one from interaction between mTOR inhabitation and an ACEi. There were no kidney allograft rejection events. ORR was seen in 46% (90%CI, 20-73) with three patients having a complete response and two having a partial response. Median DoR was 11.4 months (range, 4.9-29.7). Median PFS was 22.5 months (90%CI, 1.2-29.8), median OS was 22.5 months (90%CI, 2.9-29.8), and 3-month OS estimate was 72% (90%CI, 43-88). The median PD-L1 tumor proportion score was 1. TMB values ranged from 10 to 97, with a median of 40, and it was found that median TMB values were higher among responders (80 vs 37,  p=.05). Overall it was found that in patients with CSCC who had previous kidney transplants, Cemiplimab had some response with no kidney rejection observed.

Image: PD

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