title: Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen.
abstract: Adoptive cell transfer therapy (ACT) based on autologous tumor-infiltrating lymphocytes (TIL) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus IL2 classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL2 regimen.
  
  
  
  Twenty-five patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age < 70 years, and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL2 administered in an intravenous, continuous decrescendo regimen (ClinicalTrials.gov Identifier: NCT00937625).
  
  
  
  Classical IL2-related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor-reactive T cells. Moreover, induction and persistence of antimelanoma T-cell responses in the peripheral blood was strongly correlated to clinical response to treatment.
  
  
  
  TIL-ACT with a reduced IL2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2. Clin Cancer Res; 22(15); 3734-45. ©2016 AACR.
authors.affiliation: Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Andersen
authors.affiliation: Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Marco
authors.initials: M
authors.lastname: Donia
authors.affiliation: Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Eva
authors.initials: E
authors.lastname: Ellebaek
authors.affiliation: Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Troels Holz
authors.initials: TH
authors.lastname: Borch
authors.affiliation: Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Kongsted
authors.affiliation: Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Trine Zeeberg
authors.initials: TZ
authors.lastname: Iversen
authors.affiliation: Department of Plastic Surgery, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Lisbet Rosenkrantz
authors.initials: LR
authors.lastname: Hölmich
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Helle Westergren
authors.initials: HW
authors.lastname: Hendel
authors.affiliation: Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Özcan
authors.initials: Ö
authors.lastname: Met
authors.affiliation: Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Mads Hald
authors.initials: MH
authors.lastname: Andersen
authors.affiliation: Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Thor Straten
authors.affiliation: Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. inge.marie.svane@regionh.dk.
authors.forename: Inge Marie
authors.initials: IM
authors.lastname: Svane
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D019233:Retreatment; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007376:Interleukin-2