Immune checkpoint inhibitor therapy in HIV-associated Merkel cell carcinoma: A case series of 3 patients

Abstract

Merkel cell carcinoma (MCC) is an aggressive skin cancer, which is about twice as likely to metastasize as compared with melanoma.1 There are 2 distinct biological pathways for developing MCC: Merkel cell polyomavirus (MCPyV)-induced and ultraviolet light-induced.2 In individuals immunosuppressed by HIV infection, the risk of developing MCC is 13-fold higher than for the general population.1 Historically, outcomes have been dismal, with a 2-year disease-specific survival rate of 0% in 1 published case series.3

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 a ∼60% response rate and a durable benefit in the majority of responding patients.4 Based on these data, these 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 with anti-PD-(L)1 agents due to concerns about efficacy and potential for inadvertent augmentation of infectious and/or inflammatory activity.5 It is, therefore, unknown whether immune checkpoint inhibitors (ICI), including anti-PD-(L)1 treatment, are effective for HIV-positive patients with aMCC.

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