Pathologic Complete Response to Intralesional Interleukin-2 Therapy Associated with Improved Survival in Melanoma Patients with In-Transit Disease View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2015-06

AUTHORS

Saima Hassan, Teresa M. Petrella, Tong Zhang, Suzanne Kamel-Reid, Francesco Nordio, Andrea Baccarelli, Shachar Sade, Karen Naert, Ayman Al Habeeb, Danny Ghazarian, Frances C. Wright

ABSTRACT

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. More... »

PAGES

1950-1958

Identifiers

URI

http://scigraph.springernature.com/pub.10.1245/s10434-014-4199-z

DOI

http://dx.doi.org/10.1245/s10434-014-4199-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008174130

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25366584


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