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Abstract
Purpose: In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma.

Patients and methods: Twenty-four patients in two cohorts were enrolled and received ipilimumab at 3 mg/kg every 3 weeks for four doses in conjunction with radiation; median dose was 4,000 cGy (interquartile range, 3,550-4,800 cGy). Patients in cohort 1 were treated adjuvantly; patients in cohort 2 were treated either neoadjuvantly or as definitive therapy.

Results: Adverse event profiles were consistent with those previously reported with checkpoint inhibition and radiation. For the neoadjuvant/definitive cohort, the objective response rate was 64% (80% confidence interval, 40%-83%), with 4 of 10 evaluable patients achieving a radiographic complete response. An additional 3 patients in this cohort had a partial response and went on to surgical resection. With 2 years of follow-up, the 6-, 12-, and 24-month relapse-free survival for the adjuvant cohort was 85%, 69%, and 62%, respectively. At 2 years, all patients in the neoadjuvant/definitive cohort and 10/13 patients in the adjuvant cohort were still alive. Correlative studies suggested that response in some patients were associated with specific CD4+ T-cell subsets.

Conclusions: Overall, concurrent administration of ipilimumab and radiation was feasible, and resulted in a high response rate, converting some patients with unresectable disease into surgical candidates. Additional studies to investigate the combination of radiation and checkpoint inhibitor therapy are warranted.

Affiliations

April K S Salama  1 , Manisha Palta  2 , Christel N Rushing  3 , M Angelica Selim  4 , Kristen N Linney  5 , Brian G Czito  2 , David S Yoo  2 , Brent A Hanks  6   7 , Georgia M Beasley  8 , Paul J Mosca  8 , Chelsae Dumbauld  9 , Katelyn N Steadman  8 , John S Yi  8 , Kent J Weinhold  8 , Douglas S Tyler  10 , Walter T Lee  11 , David M Brizel  2   11
1 Department of Medicine, Division of Medical Oncology, Duke University, Durham, North Carolina. april.salama@duke.edu.
2 Department of Radiation Oncology, Duke University, Durham, North Carolina.
3 Biostatistics, Duke Cancer Institute, Durham, North Carolina.
4 Department of Pathology, Duke University, Durham, North Carolina.
5 Duke Clinical Research Institute, Durham, North Carolina.
6 Department of Medicine, Division of Medical Oncology, Duke University, Durham, North Carolina.
7 Department of Pharmacology and Cancer Biology, Durham, North Carolina.
8 Department of Surgery, Duke University, Durham, North Carolina.
9 Department of Immunology, Mayo Clinic Scottsdale, Scottsdale, Arizona.
10 Department of Surgery, The University of Texas Medical Branch at Galveston, Galveston, Texas.
11 Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham, North Carolina.