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

Abstract

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) (n = 47), RT + ICI(salvage) (n = 41) and RT(only) (n = 55) cohorts, RR(irradiated) was 70.7%, 67.5% and 43.1% (p = 0.018) while the ORR(non-irradiated) was 36.1%, 14.8% and 0.0% (p = 0.003), and the median overall survival was 18.2, 15.0 and 7.2 months, respectively (p = 0.014). Local response to RT was in all cohorts associated with longer survival (p < 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.

Keywords:

• Melanoma
• abscopal effect
• radiotherapy
• immunotherapy
• radioimmunotherapy

Authors contributions

E.B writing manuscript, data analysis, investigation, V.G RECIST assessment, H.H methodology, analysis, supervision, writing, reviewing, and editing manuscript. S.E.B, K.L and R.L supervision, reviewing and editing manuscript. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

V.G receives honoraria from Bristol Myers Squibb and Merck Sharp & Dohme.

Data availability statement

The data that support the findings of this study are available from the corresponding author E.B and specific data will be available on reasonable request.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by Swedish Cancer society; ALF grant from Region Stockholm;Cancer Research Funds of Radiumhemmet.