Radiotherapy with or without immunotherapy in metastatic melanoma: efficacy and tolerability.

Introduction: Radiotherapy (RT) is primarily considered as a palliative treatment in patients with metastatic melanoma. However, observations suggest that when RT is combined with immune checkpoint inhibitors (ICI), it can induce an immune response leading to an anti-tumoral effect also distant from the irradiated area - a phenomenon called 'abscopal effect'. The frequency and circumstances of abscopal effect among metastatic melanoma patients remains uncertain and further research is necessary.

Material And Method: This retrospective study included all metastatic melanoma patients who received non-stereotactic RT in Stockholm, Sweden in 2015-2020. Patients were grouped depending on if RT was given at start of ICI (RT + ICI(start)), at ICI progression (RT + ICI(salvage)) or without ICI (RT(only)). Response rates in irradiated (RR(irradiated)) and overall response rates in non-irradiated (ORR(non-irradiated)) metastases were evaluated together with survival and toxicity in each cohort.

Results: In the RT + ICI(start) ( = 47), RT + ICI(salvage) ( = 41) and RT(only) ( = 55) cohorts, RR(irradiated) was 70.7%, 67.5% and 43.1% ( = 0.018) while the ORR(non-irradiated) was 36.1%, 14.8% and 0.0% ( = 0.003), and the median overall survival was 18.2, 15.0 and 7.2 months, respectively ( = 0.014). Local response to RT was in all cohorts associated with longer survival ( < 0.001). The frequency of grade ≥3 immune-related adverse events was 17.0% and 19.5% in the RT + ICI(start) and RT + ICI(salvage) cohorts. No increased frequency of RT-related adverse events was seen in the RT + ICI cohorts, compared to the RT(only) cohort.

Conclusion: This retrospective study showed that melanoma patients receiving RT in combination with ICI had a superior antitumoral response in both irradiated and non-irradiated lesions as compared to patients receiving only RT. Additionally, a subgroup of patients receiving RT when progressing on ICI experienced tumor regression also in non-irradiated areas.