title: A retrospective analysis of High-Dose Interleukin-2 (HD IL-2) following Ipilimumab in metastatic melanoma.
abstract: BACKGROUND
  High dose interleukin-2 (HD IL-2) can induce durable responses in a subset of patients leading to long-term survival. Immune checkpoint blockade (ICB) has demonstrated similarly durable responses in a larger proportion of patients. However, not all patients respond to immune checkpoint blockade and subsequent therapeutic options need to be explored.
  
  
  METHODS
  The PROCLAIM database was queried for patients with metastatic melanoma who had received HD IL-2 after treatment with ipilimumab or without prior ICB. Patient characteristics, toxicity and efficacy were analyzed.
  
  
  RESULTS
  A total of 52 metastatic melanoma patients were treated with high dose IL-2 after ipilimumab and 276 patients were treated with high dose IL-2 without prior ICB. The overall response rate in the prior ipilimumab group was 21 % as compared to 12 % in the group that had not received prior ipilimumab. The median overall survival, measured from the initiation of HD IL-2 therapy, was 19.3 months in the prior ipilimumab group and 19.4 months in the no prior ICB group. Toxicities observed on HD IL-2 were relatively equivalent between the groups although there were cases of CTLA4 antibody-induced colitis reported after HD IL-2 treatment and a CTLA4 antibody-induced colitis related death.
  
  
  CONCLUSIONS
  In this retrospective analysis HD IL-2 therapy displayed antitumor activity in melanoma patients who progressed following treatment with ipilimumab. Most HD IL-2 toxicity was not worsened by prior ipilimumab therapy except for one treatment related death from colitis. Care should be taken to avoid reactivation of CTLA4 antibody-induced colitis.
authors.affiliation: Dana Farber Cancer Institute, Boston, MA USA.
authors.forename: Elizabeth I
authors.initials: EI
authors.lastname: Buchbinder
authors.affiliation: The Cancer Center - Lowell General Hospital, Lowell, MA 01854 USA.
authors.forename: Anasuya
authors.initials: A
authors.lastname: Gunturi
authors.affiliation: Prometheus Labs, 9410 Carroll Park Drive, San Diego, CA 92121 USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Perritt
authors.affiliation: Cancer Research Foundation of New York, Chappaqua, NY USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Dutcher
authors.affiliation: Prometheus Labs, 9410 Carroll Park Drive, San Diego, CA 92121 USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Aung
authors.affiliation: Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
authors.affiliation: Cleveland Clinic, Cleveland, OH USA.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
authors.affiliation: Hematology/Oncology clinic, Baton Rouge, LA USA.
authors.forename: Girald P
authors.initials: GP
authors.lastname: Miletello
authors.affiliation: Providence Health & Services, Portland, OR USA.
authors.forename: Brendan D
authors.initials: BD
authors.lastname: Curti
authors.affiliation: Moores UCSD Cancer Center, La Jolla, CA USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Daniels
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA.
authors.forename: Sapna P
authors.initials: SP
authors.lastname: Patel
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
authors.affiliation: Oncology Specialists, SC, Park Ridge, IL USA.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Hallmeyer
authors.affiliation: Loyola Medicine, Maywood, IL USA.
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.affiliation: University of Colorado, Aurora, CO USA.
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: Saint Louis University, Saint Louis, MO 63110 USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Richart
authors.affiliation: Mount Sinai Medical Center, Miami Beach, FL USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Lutzky
authors.affiliation: Duke, Durham, NC USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.affiliation: Massachusetts General Hospital, Boston, MA USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA USA.
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
keywords: Immune Checkpoint blockade; Interleukin-2; Ipilimumab; Melanoma