Utility of concurrent immunoradiation for locally advanced and/or medically inoperable melanoma and Merkel cell carcinoma.

Abstract

e21053 Background: Melanoma and Merkel Cell Carcinoma (MCC) are aggressive cutaneous malignancies with poor responses to cytotoxic chemotherapy. The use of immune checkpoint inhibitors (ICI) has substantially improved outcomes in metastatic disease and in the neoadjuvant setting. Addition of concurrent radiation therapy (RT) can augment the response of ICI, however there are little data on this combined approach as a neoadjuvant or non-operative strategy. Methods: We retrospectively analyzed outcomes of patients who received RT combined with an ICI against PD1, PD-L1, CTLA-4, or dual targets as neoadjuvant or definitive non-operative management for non-polymetastatic disease at our center from 2012 to 2018. Results: This study analyzed 14 patients, 7 males and 7 females, with a median age of 75 years. There were 10 patients with melanoma and 4 patients with MCC. Among them, 9 patients had stage III disease and 5 patients had oligometastatic disease. Prior treatments included surgery (71%), radiation (21%), and immunotherapy (21%) comprising interferon alpha (1), intralesional BCG (1), and Nivolumab (1). The ICI used were Pembrolizumab (5), Nivolumab (2), Avelumab (2), Ipilumumab (4) and Ipilumumab + Nivolumab (1). Immune related adverse events were seen in 8 patients and included endocrine (5), skin (4), and gastrointestinal (2) toxicity, majority of which were grade 1. Both grade 3 dermatitis and colitis were seen in 2 patients, and 1 patient had grade 3 colitis. There was 1 patient with grade 1 radiation dermatitis. Following concurrent ICI + RT, 4 patients who did not achieve a complete response (CR) at the irradiated site underwent surgical resection with no postoperative complications. An objective response at the irradiated site was seen in 13 (93%) patients, and 12 (86%) patients achieved a CR outside the radiated field. At the time of last follow up, 10 patients remain alive, of which 8 patients are in sustained complete remission. Conclusions: Concurrent use of ICI + RT was a safe approach in patients with locally advanced or medically inoperable melanoma and MCC with potential for durable complete remissions in the majority. Prospective studies are warranted to further validate this approach.