Safety and outcomes of combined immune checkpoint inhibitor and radiation therapy for patients with melanoma brain metastases

Abstract INTRODUCTION: In spite of the promising results of systemic treatment in melanoma, the development of brain metastases remains a common issue, often prompting use of Radiation Therapy (RT). The purpose of this study is to assess the safety and outcomes of Immune Checkpoint Inhibitor (ICI) and brain RT with a focus on timing of both treatments. METHODS This retrospective study included all consecutive patients treated for a brain metastatic melanoma with an ICI (anti – CTLA4 or anti – PD1 or both) and brain RT from December 1, 2010 and April 30, 2018. The concurrent group was defined by an ICI performed within 4 weeks before or after RT. Primary endpoint was neurological adverse events graded with Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS Fifty - three consecutive patients were included. A total of 81 RT courses were performed: 23 with whole brain radiotherapy (WBRT) and 58 with stereotactic radiotherapy (SRT). The majority of RT (63%, n = 51) was delivered with concurrent ICI. Acute neurological Adverse Events (AE) ≥ grade 3 occurred for 12.3% of RT course, with no difference between concurrent and non – concurrent groups. The median OS after RT was 11.5 months for the entire cohort with 15.9 months for SRT in comparison to 2.7 months for WBRT. The objective response rate was significantly better for concurrent ICI – SRT group at 66.7% compared to 40% for non-– concurrent group (p = 0.04). One-year LC probability was higher in the concurrent group than in the non-concurrent group, respectively 72. % vs 38.5% (p = 0.007). CONCLUSIONS Combined RT and ICI is well tolerated with acceptable neurological adverse events. Stereotactic radiation therapy delivered concurrently with ICI is associated with improved local control.