Merkel cell carcinoma in solid organ transplant recipients: prognosis and response to immunotherapy.

Abstract

Merkel cell carcinoma (MCC) is an aggressive skin cancer with an increased risk of occurrence in immunocompromised patients, including solid organ transplant recipients (SOTRs). As the number of SOTRs rises worldwide, MCC cases in this population are also expected to increase. While anti-programmed cell death 1 ligand 1 (anti-PD-L1; also known as anti-programmed death ligand 1) immunotherapy generates durable tumour responses in ∼50% of immunocompetent (IC) patients with advanced MCC, its efficacy and safety in SOTRs remain uncertain as these patients have been excluded from most clinical trials. To compare baseline characteristics and outcomes among SOTRs and IC patients with MCC, and to evaluate the efficacy and toxicity of anti-PD-L1 in SOTRs. We queried an MCC registry from our institution (April 1988-May 2024), extracting data on demographics, anti-PD-L1 response and immunosuppression regimens, along with incidence of allograft rejection and failure, for analysis. We identified 1214 patients with MCC (37 SOTRs and 1177 IC patients); 8 of 37 SOTRs received anti-PD-L1. Median time from SOT to MCC diagnosis was 10 years (range 0.4-43). The proportion of patients with advanced MCC (≥ stage III) was 76% in SOTRs compared with 51% in IC patients (P = 0.004). SOTR status was associated with worse outcomes, including higher rates of disease progression [adjusted hazard ratio (aHR) 2.3], MCC-specific mortality (aHR 3.0) and overall mortality (aHR 3.9) (all P < 0.001 for the respective comparisons). Median time to death due to MCC for SOTRs was 2.7 years; 24% of SOTRs died within one year of diagnosis, in contrast with just 4% of IC patients. Median time to MCC progression for SOTRs was 8.6 months vs. 12 years for IC patients. Among SOTRs, 70% developed distant metastases within 2 years vs. 25% of IC patients. All eight MCC SOTRs treated with anti-PD-L1 were kidney transplant recipients, with five (63%) experiencing an objective response (two complete response, three partial response). However, two patients (29%) experienced irreversible graft failure within 9 weeks. SOTR status is a significant independent risk factor of a worse prognosis for MCC. This study represents the largest cohort evaluating the efficacy and safety of anti-PD-L1 in SOTRs with advanced MCC, highlighting the potential benefits in this population.