Abscopal Response in Metastatic Melanoma: Real-World Data of a Retrospective, Multicenter Study

SIMPLE SUMMARY: An abscopal response (AR) is a rare phenomenon defined as a distant response outside of the radiation field. It opens up the perspective of “in situ” vaccination of cancer. This phenomenon is rare and its mechanisms are unknown. In metastatic melanoma (MM), the approach regarding the efficacy of immunotherapy is to not use immunotherapy as a tool for enhancing radiation response but rather as one that needs to be integrated into immunotherapy to potentiate the specific effects of immunotherapy. The aim of our retrospective study was to investigate the incidence of the AR and its impact on therapeutic outcomes in a homogeneous population of patients with MM and a control group, to identify the factors associated with the AR. AR in metastatic melanoma seems highly prognostic of overall survival although it is a rare phenomenon. Factors associated with AR have been identified. ABSTRACT: Objective: To evaluate the incidence of the abscopal response (AR) in patients with metastatic melanoma requiring palliative radiotherapy (RT). Patients and methods: Patients treated for metastatic melanoma between January 1998 and February 2020 in four oncology departments were screened. Patients with progression under immune checkpoint inhibitors or without ongoing systemic treatment, and requiring palliative RT were considered. The AR was defined as an objective response according to RECIST and/or iRECIST for at least one non-irradiated metastasis at distance (≥10 cm) from the irradiated lesion. Primary endpoint was the rate of AR. Secondary endpoints were overall survival (OS), progression-free survival (PFS), local control (LC) of the irradiated lesion, and toxicity as assessed by CTCAE v5. Results: Over the period considered, 118 patients were included and analyzed. Fifteen patients (12.7%) had an AR. With a median follow-up of 7.7 months (range, 0.2–242.2), median OS and PFS after RT were significantly longer in patients with an AR compared to those without: 28 vs. 6.6 months (p < 0.01) and not reached vs. 3.2 months, respectively. No grade ≥2 toxicity was reported. Patients who developed an AR were more likely to be treated with immunotherapy (93.3% vs. 55.9%, p = 0.02). In multivariate analysis, they had a higher number of irradiated metastases treated concomitantly (HR = 16.9, p < 0.01) and a higher rate of mild infections during RT (HR = 403.5, p < 0.01). Conclusions: AR in metastatic melanoma seems to be highly prognostic of overall survival, although it is a rare phenomenon. It may be promoted by multiple concomitant treatments with RT and immunotherapy and by acute inflammatory events such as infection.