TY - JOUR
T1 - Ipilimumab and radiation in patients with high-risk resected or regionally advanced Melanoma
AU - Salama, April K.S.
AU - Palta, Manisha
AU - Rushing, Christel N.
AU - Selim, M. Angelica
AU - Linney, Kristen N.
AU - Czito, Brian G.
AU - Yoo, David S.
AU - Hanks, Brent A.
AU - Beasley, Georgia M.
AU - Mosca, Paul J.
AU - Dumbauld, Chelsae
AU - Steadman, Katelyn N.
AU - Yi, John S.
AU - Weinhold, Kent J.
AU - Tyler, Douglas S.
AU - Lee, Walter T.
AU - Brizel, David M.
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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 CD4þ 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.
AB - 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 CD4þ 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.
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U2 - 10.1158/1078-0432.CCR-20-2452
DO - 10.1158/1078-0432.CCR-20-2452
M3 - Article
C2 - 33172894
AN - SCOPUS:85102508563
SN - 1078-0432
VL - 27
SP - 1287
EP - 1295
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -