title: Single Institution Experience of Ipilimumab 3 mg/kg with Sargramostim (GM-CSF) in Metastatic Melanoma.
abstract: Ipilimumab, 10 mg/kg with sargramostim (GM-CSF; GM), improved overall survival (OS) and safety of patients with advanced melanoma over ipilimumab in a randomized phase II trial. The FDA-approved dose of ipilimumab of 3 mg/kg has not been assessed with GM (IPI-GM). Consecutive patients treated with IPI-GM at a single institution were reviewed. Treatment included ipilimumab every 3 weeks × 4 and GM, 250-μg s.c. injection days 1 to 14 of each ipilimumab cycle. Efficacy, clinical characteristics, toxicities, and blinded radiology review of tumor burden were evaluated. Thirty-two patients were identified with 25 (78%) having immune-related response criteria (irRC) measurable disease and 41% with central nervous system metastases. A total of 88.6% of GM doses were administered. Response rate by irRC and disease control rate at 12 weeks were 20% and 44%, respectively (median follow-up 37 weeks). Immune-related adverse events (irAE) were observed in 10 (31.3%) patients, with 3 (9.4%) grade 3 events. Patients with grade 3 irAEs had prior autoimmunity, advanced age, and poor performance status. The median OS from first dose of ipilimumab was 41 weeks. Ipi-GM treatment is feasible and in this poor-risk advanced melanoma population, efficacy appeared similar but safety appeared improved relative to historical ipilimumab alone.
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois. jluke@medicine.bsd.uchicago.edu.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Luke
authors.affiliation: Melanoma Disease Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Hilary
authors.initials: H
authors.lastname: Donahue
authors.affiliation: Department of Radiology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts. Harvard Medical School, Boston, Massachusetts.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Nishino
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.affiliation: Melanoma Disease Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Meredith
authors.initials: M
authors.lastname: Davis
authors.affiliation: Melanoma Disease Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Nancy
authors.initials: N
authors.lastname: Bailey
authors.affiliation: Melanoma Disease Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Harvard Medical School, Boston, Massachusetts.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Ott
authors.affiliation: Melanoma Disease Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Harvard Medical School, Boston, Massachusetts.
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000556:secondary; D004334:Drug Administration Schedule; D004341:Drug Evaluation / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary*; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab; D011994:Recombinant Proteins; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor