Case Report: Exceptional Response to Avelumab After Failure of Electrochemotherapy in a Patient With Rapidly Progressive, PD-L1-Negative Merkel Cell Carcinoma

Abstract

This case report shows, for the first time, a patient experiencing a complete response after one dose of avelumab following extensive disease progression with prior electrochemotherapy (ECT) treatment. We suggest that ECT may help to establish a tumor microenvironment favorable to immunotherapy. Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with seldom durable chemotherapy responses. ECT has recently emerged as a potential treatment option for several malignancies, including MCC. Avelumab, an anti-programmed cell death-ligand 1 (PD-L1) monoclonal antibody, became the first approved treatment for patients with metastatic MCC. ECT has been shown to activate the immune response, but it is still unknown how ECT may affect patient’s response to subsequent immunotherapy. We report a case of a patient with MCC who presented with a rapidly growing skin nodule of the right cheek and experienced extensive disease progression following surgical debulking and ECT treatment. The patient received a flat dose of 800 mg avelumab intravenously every 2 weeks showing complete tumor regression after only one dose. Immunohistochemical analysis of surgical and post-ECT biopsies collected from the primary lesion revealed tumor expression of programmed cell death protein-1 (PD-1), but not PD-L1. Analysis of the tumor samples also revealed no expression of Merkel cell polyomavirus (MCPyV). Comparison of the biopsies showed a decrease in myeloid and T-cell markers after ECT but an increase in major histocompatibility complex (MHC) class I expression on tumor cells. Additionally, the patient experienced an increase in neutrophil-to-lymphocyte ratio and lactate dehydrogenase values post-ECT, which subsequently decreased with avelumab treatment. As of 30 October 2019, the patient was still receiving avelumab treatment and had an ongoing complete response. In this case report, a patient with PD-L1-negative and MCPyV-negative MCC who had disease progression following ECT experienced complete tumor regression with avelumab treatment, suggesting, for the first time to our knowledge, that ECT may help to establish a tumor microenvironment favorable to immunotherapy via a potential abscopal effect. Tumor-intrinsic PD-1 expression and modulation of MHC class I antigens after ECT may contribute to the clinical efficacy of avelumab in this context.

Palliative Treatment of Esophageal Cancer Using Calcium Electroporation

“…The survival prognosis is poor, with an expected five-year survival of only 20%, with many of the patients already having distant metastases when diagnosed. In individual patient cases [ 29 , 30 ] and in preclinical studies with both ECT with bleomycin and CaEP [ 31 , 32 , 33 , 34 ] the treatment has been shown to induce a systemic immunological response. This is interesting, as CaEP and/or ECT may hold the potential of going from a local treatment only to a systemic treatment in the future.…”

“…Even more interesting, it has been suggested that ECT, followed by an immunological treatment, might lead to an even more convincing tumor response [ 35 ]. In a single case, a patient with highly aggressive skin cancer was treated with ECT followed by one dose of Avelumab (anti-programmed death-ligand 1 (PD-L1) monoclonal antibody) and experienced an excellent treatment response [ 30 ]. It was suggested that ECT helped to establish a favorable microenvironment in the malignant cells, which further enhanced the effect of the Avelumab.…”

An Updated Review of the Biomarkers of Response to Immune Checkpoint Inhibitors in Merkel Cell Carcinoma: Merkel Cell Carcinoma and Immunotherapy

“…Also, additional effort has been made to understand the prognostic and predictive potential of the NLR and LDH biomarkers in patients with MCC [123]. Torchio and his group examined an interesting case of a patient who had elevated NLR and LDH values prior to ICI treatment, followed by a rapid decrease in the levels of these markers after therapy [123]. An exceptionally complete response from the patient was reported.…”