title: Pathologic complete response to intralesional interleukin-2 therapy associated with improved survival in melanoma patients with in-transit disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada.
authors.forename: Saima
authors.initials: S
authors.lastname: Hassan
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Petrella
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Francesco
authors.initials: F
authors.lastname: Nordio
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.forename: Shachar
authors.initials: S
authors.lastname: Sade
authors.forename: Karen
authors.initials: K
authors.lastname: Naert
authors.forename: Ayman Al
authors.initials: AA
authors.lastname: Habeeb
authors.forename: Danny
authors.initials: D
authors.lastname: Ghazarian
authors.forename: Frances C
authors.initials: FC
authors.lastname: Wright
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2