Cemiplimab for Kidney Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma

Abstract

Purpose: Cemiplimab is approved for treating locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC). Solid organ transplant recipients have been excluded from immunotherapy trials, given concern for allograft rejection despite their increased risk of skin cancers. Chronic immunosuppression is necessary to prevent organ rejection but may attenuate antitumor response with PD-1 inhibitors.

Methods: We report a phase I study of cemiplimab for kidney transplant recipients (KTRs) with advanced CSCC. After cross-taper to a mammalian target of rapamycin (mTOR) inhibitor and pulsed dose corticosteroids (prednisone 40 mg once daily, the day before and on days 1-3 of each cycle, followed by 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 were assessed for response every 8 weeks. The primary end point was the rate of kidney rejection, with key secondary end points including rate and duration of response, and survival.

Results: Twelve patients were treated. No kidney rejection or loss was observed. A response to cemiplimab was observed in five of 11 evaluable patients (46%; 90% CI, 22 to 73), including two with durable responses beyond a year. Median follow-up was 6.8 months (range, 0.7-29.8). Treatment-related grade 3 or greater adverse events occurred in five patients (42%), including diarrhea, infection, and metabolic disturbances. One patient died of angioedema and anaphylaxis attributed to mTOR inhibitor cross-taper.

Conclusion: mTOR inhibitor and corticosteroids represent a favorable immunosuppressive regimen for KTRs with advanced CSCC receiving immunotherapy. This combination resulted in durable antitumor responses with no kidney rejection events (funded by Regeneron Pharmaceuticals [ClinicalTrials.gov identifier: NCT04339062]).

FIG 1.

(A) Waterfall plot depicting best overall response (RECIST v1.1) to cemiplimab treatment. Each column represents an individual patient. (B) Swimmer plot showing time on cemiplimab treatment and follow-up period; each row represents an individual patient. (C) Spider plot showing the percentage change (RECIST v1.1) in tumor measurements over time; each line represents an individual patient. (D) Pretreatment (left) and post-treatment (right) CT images showing an infiltrative right preauricular mass from CSCC that resolved over time. Fused PET and CT scans with false color added showing a left dorsal nose CSCC before (left) and after (right) cemiplimab treatment. Fused PET and CT scans showing right level II neck adenopathy (left) before and after (right) treatment. ^aDenotes the development of a new lesion at first response assessment. BL, baseline; CSCC, cutaneous squamous cell carcinoma; CT, computed tomography; PET, positron emission tomography.

FIG 2.

Kaplan-Meier curves plotting the probability of (A) PFS and (B) OS among kidney transplant recipients with advanced cutaneous squamous cell carcinoma receiving cemiplimab. OS, overall survival; PFS, progression-free survival.

FIG 3.

(A) Tumor mutational burden (mutations per megabase) and PD-L1 TPS plotted for patients with evaluable pretreatment tumor samples arranged by best response to treatment (complete or partial response reflects responders; progressive disease reflects nonresponders). (B) Tumor mutational plot depicting gene alterations among each patient (columns) with evaluable pretreatment tumor material for targeted next-generation sequencing arranged by best response to treatment (only those mutations occurring in at least 20% of samples are depicted). (C) Summary plot of baseline and monthly on-treatment Signatera ctDNA values (MTM/mL) for four participants with available testing results. Patient numerical identifier shown in the legend and color-coded by best overall response (red = responder; blue = unevaluable). (D) In-depth multiparametric immune profiling by flow cytometry on matched or paired blood and tumor specimens before (pre-) and on (post-)treatment separated by response to immunotherapy. ctDNA, circulating tumor DNA; ID, identifier; MTM/ml, mean tumor molecules per mL; NR, nonresponder; R, responder; SNV, singe-nucleotide variant; TPS, tumor proportion score.

FIG A1.

Patient screening and allocation diagram.

FIG A2.

(A) Graphical plot showing serum creatinine (mg/dL) trend over time from baseline and while on treatment at monthly intervals for all study participants (arranged by participant identifier with annotation for significant events). (B) Prospera dd-cfDNA (%) plotted over time from study baseline (in weeks) for participants with available testing (N = 5; arranged by participant identifier). cfDNA, cell-free DNA; dd, donor-derived.