Ipilimumab and Radiation in Patients with High-risk Resected or Regionally Advanced Melanoma

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. Twenty-four patients in two cohorts were enrolled and received ipilimumab at 3 mg/kg...

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Bibliographic Details
Published in:	Clinical cancer research Vol. 27; no. 5; pp. 1287 - 1295
Main Authors:	Salama, April K S, Palta, Manisha, Rushing, Christel N, Selim, M Angelica, Linney, Kristen N, Czito, Brian G, Yoo, David S, Hanks, Brent A, Beasley, Georgia M, Mosca, Paul J, Dumbauld, Chelsae, Steadman, Katelyn N, Yi, John S, Weinhold, Kent J, Tyler, Douglas S, Lee, Walter T, Brizel, David M
Format:	Journal Article
Language:	English
Published:	United States 01-03-2021
Subjects:	Adult Aged Aged, 80 and over Antineoplastic Agents, Immunological - therapeutic use Chemoradiotherapy, Adjuvant - mortality Feasibility Studies Female Follow-Up Studies Humans Ipilimumab - therapeutic use Male Melanoma - pathology Melanoma - therapy Middle Aged Neoadjuvant Therapy - mortality Neoplasm Recurrence, Local - pathology Neoplasm Recurrence, Local - therapy Prognosis Prospective Studies Radiotherapy Dosage Survival Rate Young Adult
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Summary:	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. 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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Authors’ Contributions A.K.S. Salama: Conceptualization, resources, formal analysis, funding acquisition, investigation, writing-original draft. M. Palta: Conceptualization, supervision, investigation, writing-original draft, writing-review and editing. C.N. Rushing: Data curation, formal analysis, writing-original draft, writing-review and editing. M.A. Selim: Data curation, investigation, writing-review and editing, pathologist who reviewed clinical specimens and performed staining of slides. K.N. Linney: Data curation, project administration, writing-review and editing. B.G. Czito: Data curation, investigation, writing-review and editing. D.S. Yoo: Data curation, investigation, writing-review and editing. B.A. Hanks: Data curation, investigation, writing-review and editing. G.M. Beasley: Data curation, investigation, writing-review and editing. P.J. Mosca: Data curation, investigation, writing-review and editing. C. Dumbauld: Data curation, formal analysis, investigation. K.N. Steadman: Data curation, formal analysis, investigation. J.S. Yi: Data curation, formal analysis, investigation, writing-original draft. K.N. Weinhold: Conceptualization, resources, supervision, writing-review and editing. D.S. Tyler: Conceptualization, resources, funding acquisition, investigation, writing-review and editing. W.T. Lee: Conceptualization, resources, formal analysis, supervision, writing-review and editing. D.M. Brizel: Conceptualization, supervision, funding acquisition, investigation, writing-original draft, writing-review and editing.
ISSN:	1078-0432 1557-3265
DOI:	10.1158/1078-0432.CCR-20-2452