title: A phase I/IIa clinical trial in stage IV melanoma of an autologous tumor-dendritic cell fusion (dendritoma) vaccine with low dose interleukin-2.
abstract: BACKGROUND
  Stage IV melanoma has high mortality, largely unaffected by traditional therapies. Immunotherapy including cytokine therapies and checkpoint inhibitors improves outcomes, but has significant toxicities. In this phase I/IIa trial, we investigated safety and efficacy of a dendritoma vaccine, an active, specific immunotherapy, in stage IV melanoma patients.
  
  
  METHODS
  Autologous tumor lysate and dendritic cells were fused creating dendritoma vaccines for each patient. Phase I patients were vaccinated every 3 months with IL-2 given for 5 days after initial inoculation. Phase IIa patients were vaccinated every 6 weeks with IL-2 given on days 1, 3 and 5 after initial inoculation. Toxicity and clinical outcomes were assessed.
  
  
  RESULTS
  Twenty-five patients were enrolled and inoculated. All dendritoma and IL-2 toxicities were <grade 3. Median overall survival (OS) was 16.1 months with projected 5-year survival = 29 %. Significant OS improvement for patients receiving ≥3 versus <3 inoculations (43.1 vs. 16.7 %, p = 0.02) was observed. Patients with no evidence of disease (NED) showed improved OS (80 vs. 14 %, p = 0.005). No clinicopathologic differences were present between phase I (n = 10) and IIa (n = 15) patients; phase IIa patients received more frequent dosing and higher mean number of inoculations. Phase IIa median OS was significantly higher (23.8 vs. 8.7 months, p = 0.004).
  
  
  CONCLUSIONS
  The dendritoma vaccine has minimal toxicity profile with potential clinical benefit. There was OS advantage for NED stage IV patients, those receiving higher number of doses and increased frequency. Based on these results, we initiated a phase IIb trial utilizing improved dendritoma technology in the adjuvant setting for NED stage III/IV melanoma patients.
authors.affiliation: General Surgery Department, San Antonio Military Medical Center, 3851 Roger Brooke Drive, Joint Base San Antonio-Ft. Sam Houston, TX, USA.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Greene
authors.affiliation: General Surgery Department, San Antonio Military Medical Center, 3851 Roger Brooke Drive, Joint Base San Antonio-Ft. Sam Houston, TX, USA.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Schneble
authors.affiliation: General Surgery Department, San Antonio Military Medical Center, 3851 Roger Brooke Drive, Joint Base San Antonio-Ft. Sam Houston, TX, USA.
authors.forename: Doreen O
authors.initials: DO
authors.lastname: Jackson
authors.affiliation: General Surgery Department, San Antonio Military Medical Center, 3851 Roger Brooke Drive, Joint Base San Antonio-Ft. Sam Houston, TX, USA. diane.f.hale.mil@mail.mil.
authors.forename: Diane F
authors.initials: DF
authors.lastname: Hale
authors.affiliation: General Surgery Department, San Antonio Military Medical Center, 3851 Roger Brooke Drive, Joint Base San Antonio-Ft. Sam Houston, TX, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vreeland
authors.affiliation: General Surgery Department, San Antonio Military Medical Center, 3851 Roger Brooke Drive, Joint Base San Antonio-Ft. Sam Houston, TX, USA.
authors.forename: Madeline
authors.initials: M
authors.lastname: Flores
authors.affiliation: General Surgery Department, San Antonio Military Medical Center, 3851 Roger Brooke Drive, Joint Base San Antonio-Ft. Sam Houston, TX, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Martin
authors.affiliation: General Surgery Department, San Antonio Military Medical Center, 3851 Roger Brooke Drive, Joint Base San Antonio-Ft. Sam Houston, TX, USA.
authors.forename: Garth S
authors.initials: GS
authors.lastname: Herbert
authors.affiliation: General Surgery Department, Madigan Army Medical Center, 9040 Jackson Ave., Tacoma, 98431, WA, USA.
authors.forename: Mark O
authors.initials: MO
authors.lastname: Hardin
authors.affiliation: Clemson University, Clemson, SC, USA.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Perseus PCI, Greenville, SC, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wagner
authors.affiliation: Cancer Vaccine Development Program, 600 Navarro Street, Suite 500, San Antonio, TX, 78205, USA. georgepeoples2@hotmail.com.|Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. georgepeoples2@hotmail.com.
authors.forename: George E
authors.initials: GE
authors.lastname: Peoples
mesh_terms: D000368:Aged; D018771:Arthralgia / Q000139:chemically induced; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D023341:Chills / Q000139:chemically induced; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004890:Erythema / Q000139:chemically induced; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D007376:Interleukin-2
keywords: Adjuvant; Dendritic cell; Dendritoma; Melanoma; Vaccine