title: Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy.
abstract: OBJECTIVE
  Most treatments for patients with metastatic melanoma have a low rate of complete regression and thus overall survival in these patients is poor. We investigated the ability of adoptive cell transfer utilizing autologous tumor-infiltrating lymphocytes (TIL) to mediate durable complete regressions in heavily pretreated patients with metastatic melanoma.
  
  
  METHODS
  Ninety-three patients with measurable metastatic melanoma were treated with the adoptive transfer of autologous TILs administered in conjunction with interleukin-2 following a lymphodepleting preparative regimen on three sequential clinical trials. Ninety-five percent of these patients had progressive disease following a prior systemic treatment. Median potential follow-up was 62 months.
  
  
  RESULTS
  Objective response rates by Response Evaluation Criteria in Solid Tumors (RECIST) in the 3 trials using lymphodepleting preparative regimens (chemotherapy alone or with 2 or 12 Gy irradiation) were 49%, 52%, and 72%, respectively. Twenty of the 93 patients (22%) achieved a complete tumor regression, and 19 have ongoing complete regressions beyond 3 years. The actuarial 3- and 5-year survival rates for the entire group were 36% and 29%, respectively, but for the 20 complete responders were 100% and 93%. The likelihood of achieving a complete response was similar regardless of prior therapy. Factors associated with objective response included longer telomeres of the infused cells, the number of CD8(+)CD27(+) cells infused, and the persistence of the infused cells in the circulation at 1 month (all P(2) < 0.001).
  
  
  CONCLUSIONS
  Cell transfer therapy with autologous TILs can mediate durable complete responses in patients with metastatic melanoma and has similar efficacy irrespective of prior treatment. Clin Cancer Res; 17(13); 4550-7. ©2011 AACR.
authors.affiliation: Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA. sar@nih.gov
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
authors.forename: Udai S
authors.initials: US
authors.lastname: Kammula
authors.forename: Marybeth S
authors.initials: MS
authors.lastname: Hughes
authors.forename: Giao Q
authors.initials: GQ
authors.lastname: Phan
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Citrin
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
authors.forename: John R
authors.initials: JR
authors.lastname: Wunderlich
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Morton
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Laurencot
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Donald E
authors.initials: DE
authors.lastname: White
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D016019:Survival Analysis; D016615:Telomere / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult