PURPOSE: Melanoma patients with in-transit disease have a high mortality rate despite various treatment strategies. The aim of this study was to validate the role of intralesional interleukin (IL)-2, to understand its mechanism of action, and to better understand factors that may influence its response. METHODS: We retrospectively collected the clinicopathological data of 31 consecutive patients who presented to a tertiary care cancer center for treatment of in-transit melanoma with intralesional IL-2. Kaplan-Meier survival curves and multivariable Cox regression analysis were performed. Immunohistochemistry (IHC) was used to better understand the immune response to localized IL-2 therapy. Targeted next-generation sequencing was performed to genomically characterize the tumors. RESULTS: Ten patients (10/31, 32 %) achieved a pathologic complete response (pCR), 17/21 (55 %) had a partial response, and 4/21 (19 %) had progressive disease on treatment. pCR to IL-2 therapy was associated with overall survival (log-rank p = 0.004) and improved progression-free survival (PFS) [adjusted hazard ratio (HR) 0.11; 95 % CI 0.02-0.47; p = 0.003). A higher CD8+ T cell infiltrate was identified in in-transit lesions with a pCR compared with the other lesions (mean IHC score 3.78 vs. 2.61; p = 0.01). Patients with an elevated CD8+ infiltrate demonstrated an improved PFS (unadjusted HR 0.08; 95 % CI 0.01-0.52; p = 0.008). CONCLUSIONS: Thirty-two percent of patients achieved pCR with intralesional IL-2 therapy and had a significantly improved PFS compared with the rest of the cohort, which may be explained by a systemic CD8+ T-cell response.
PURPOSE:Melanomapatients with in-transit disease have a high mortality rate despite various treatment strategies. The aim of this study was to validate the role of intralesional interleukin (IL)-2, to understand its mechanism of action, and to better understand factors that may influence its response. METHODS: We retrospectively collected the clinicopathological data of 31 consecutive patients who presented to a tertiary care cancer center for treatment of in-transit melanoma with intralesional IL-2. Kaplan-Meier survival curves and multivariable Cox regression analysis were performed. Immunohistochemistry (IHC) was used to better understand the immune response to localized IL-2 therapy. Targeted next-generation sequencing was performed to genomically characterize the tumors. RESULTS: Ten patients (10/31, 32 %) achieved a pathologic complete response (pCR), 17/21 (55 %) had a partial response, and 4/21 (19 %) had progressive disease on treatment. pCR to IL-2 therapy was associated with overall survival (log-rank p = 0.004) and improved progression-free survival (PFS) [adjusted hazard ratio (HR) 0.11; 95 % CI 0.02-0.47; p = 0.003). A higher CD8+ T cell infiltrate was identified in in-transit lesions with a pCR compared with the other lesions (mean IHC score 3.78 vs. 2.61; p = 0.01). Patients with an elevated CD8+ infiltrate demonstrated an improved PFS (unadjusted HR 0.08; 95 % CI 0.01-0.52; p = 0.008). CONCLUSIONS: Thirty-two percent of patients achieved pCR with intralesional IL-2 therapy and had a significantly improved PFS compared with the rest of the cohort, which may be explained by a systemic CD8+ T-cell response.
Authors: F C Wright; S Kellett; N J Look Hong; A Y Sun; T P Hanna; C Nessim; C A Giacomantonio; C F Temple-Oberle; X Song; T M Petrella Journal: Curr Oncol Date: 2020-06-01 Impact factor: 3.677
Authors: Maryam Pourmaleki; Caitlin J Jones; Charlotte E Ariyan; Zheng Zeng; Mono Pirun; Daniel A Navarrete; Yanyun Li; Mianlei Zhang; Subhiksha Nandakumar; Carl Campos; Saad Nadeem; David S Klimstra; Claire F Temple-Oberle; Thomas Brenn; Evan J Lipson; Kara M Schenk; Julie E Stein; Janis M Taube; Michael G White; Raymond Traweek; Jennifer A Wargo; John M Kirkwood; Billel Gasmi; Stephanie L Goff; Alex D Corwin; Elizabeth McDonough; Fiona Ginty; Margaret K Callahan; Andrea Schietinger; Nicholas D Socci; Ingo K Mellinghoff; Travis J Hollmann Journal: Cancer Immunol Res Date: 2022-03-01 Impact factor: 12.020