Cemiplimab for kidney transplant recipients with advanced squamous cell carcinoma of the skin.

Key message:

In this phase I clinical trial, renal transplant recipients with advanced or metastatic squamous cell skin cancer were treated with cemiplimab after crossover to an mTOR inhibitor and steroids. The primary endpoint focused on the incidence of renal rejection. Among the 12 patients treated, none experienced renal rejection, and 46% achieved an objective response to cemiplimab. However, 42% of patients experienced grade 3 or higher adverse events, and one patient died due to angioedema and anaphylaxis associated with mTOR inhibitor crossover.

Although immune checkpoint inhibitors have traditionally been considered risky for solid organ transplant patients, the results of this phase I study suggest that the use of an mTOR inhibitor may be beneficial in preventing allograft rejection after immune checkpoint inhibitor therapy in solid organ transplant recipients with metastatic cancer. .

Summary:

Target

Cemiplimab is approved for the treatment of locally advanced or metastatic squamous cell carcinoma (CSCC). Solid organ transplant recipients have been excluded from immunotherapy trials due to concerns about allograft rejection, despite an increased risk of skin cancer. Chronic immunosuppression is necessary to prevent organ rejection but may attenuate the antitumor response with PD-1 inhibitors.

Methods

We report a phase I study of cemiplimab in kidney transplant recipients (KTRs) with advanced CSCC. After switching to a target of rapamycin (mTOR) inhibitor and pulsatile corticosteroids (prednisone 40 mg once daily the night before and on days 1–3 of each cycle, then 20 mg once daily on days 4–6, then 10 mg once daily until the day before each subsequent cycle), patients received cemiplimab 350 mg intravenously once every 3 weeks for up to 2 years, and response was assessed every 8 weeks. The primary endpoint was the incidence of renal rejection, and key secondary endpoints were response rate and duration, and survival.

Results

Twelve patients were treated. No renal rejection or loss was observed. Response to cemiplimab was observed in five of 11 patients assessed (46%; 90% CI 22 to 73), including two with sustained response at one year. The mean follow-up duration was 6.8 months (range 0.7–29.8). Treatment-related adverse events of grade 3 or higher were observed in five patients (42%), including diarrhea, infection, and metabolic abnormalities. One patient died from angioedema and anaphylaxis associated with mTOR inhibitor cross-reduction.

conclusions

mTOR inhibitors and corticosteroids represent a beneficial immunosuppressive regimen for renal transplant recipients with advanced CSCC receiving immunotherapy. This combination resulted in a sustained antitumor response with no incidence of kidney rejection.

Fountain: BioPress