Immune checkpoint inhibitor therapy in HIV-associated Merkel cell carcinoma: a case series of three patients

Abstract

Introduction: Merkel cell carcinoma (MCC) is an aggressive skin cancer that is about twice as likely to metastasize as compared to melanoma. There are two distinct biological pathways for developing MCC: Merkel cell polyomavirus (MCPyV) induced and ultraviolet (UV) light induced. In individuals immunosuppressed by HIV infection, the risk of developing MCC is 13-fold higher than for the general population; outcomes have been historically dismal with a 2-year disease-specific survival rate of 0% among one published case series. Recently, anti-programmed cell death-1 (PD-1) and anti-programmed death ligand-1 (PD-L1) agents in immunocompetent patients with advanced MCC (aMCC) demonstrated ~60% response rate and durable benefit in majority of cases. Based on the data, those agents have emerged as the treatment of choice for aMCC. However, immunosuppressed individuals, including those who are HIV-positive, have been excluded from clinical trials of anti-PD-(L)1 agents due to concerns about efficacy and potential for inadvertent augmentation of infectious and/or inflammatory activity. It is therefore unknown whether immune checkpoint inhibitors (ICI), including anti-PD-(L)1 treatment, are effective for HIV-positive patients with aMCC.

Materials and Method: To better understand the clinical and biological features of HIV-positive aMCC patients treated with ICIs, we performed a comprehensive review of our Seattle-based IRB-approved repository of MCC patient data and specimens. We also describe biomarker analyses including immune cell infiltration, tumor MCPyV status, and intratumoral expression of PD-1 and PD-L1.

Result: Among the ~1500 MCC patients diagnosed between 1980-2020, we identified 10 patients with a history of HIV at the time of their MCC diagnosis. All 10 patients eventually developed distant metastatic disease. Among these patients, three were treated with ICI therapy