title: Characterizing the clinical benefit of ipilimumab in patients who progressed on high-dose IL-2.
abstract: Ipilimumab improves overall survival (OS) in patients with metastatic melanoma including those previously treated with high-dose interleukin-2 (HD IL-2). The primary objective of this study was to determine if clinical response or progression-free survival (PFS) to HD IL-2 could predict benefit to subsequent ipilimumab. The secondary objective was to further characterize the clinical benefit of ipilimumab in patients who have progressed on HD IL-2. We reviewed the records of all patients with metastatic melanoma who received HD IL-2 at MD Anderson Cancer Center or Beth Israel Deaconess Medical Center from 2003 to 2009 and further identified patients who also received ipilimumab after progressing on HD IL-2. OS to ipilimumab was calculated from the first dose of ipilimumab, determined by Kaplan-Meier analysis, and was compared in patients based on their prior clinical response and PFS to HD IL-2 using the log-rank test. Patients were grouped based on their prior response to HD IL-2 as follows: complete response and partial response, stable disease, and progressive disease. Patients were also grouped and compared by prior PFS to HD IL-2 in >60 days versus ≤60 days. A total of 208 patients with melanoma were treated with HD IL-2, 130 (63%) received additional systemic therapy after confirmed disease progression, and 48 (23%) received ipilimumab. The clinical benefit of ipilimumab was similar to previously published results (OS, 12.0 mo; PFS, 2.5 mo; response rate, 16.7%). Prior clinical response or PFS to HD IL-2 did not predict benefit to subsequent ipilimumab. Prospective trials of HD IL-2 followed by ipilimumab could potentially identify patients most likely to benefit from a sequential approach of HD IL-2 followed by ipilimumab.
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Joseph
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Eckel-Passow
authors.forename: Ruchi
authors.initials: R
authors.lastname: Sharma
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Alexander
authors.initials: A
authors.lastname: Parker
authors.forename: John
authors.initials: J
authors.lastname: Jakob
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Buchbinder
authors.forename: Roland L
authors.initials: RL
authors.lastname: Bassett
authors.forename: Michael A
authors.initials: MA
authors.lastname: Davies
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality*; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007376:Interleukin-2; D000074324:Ipilimumab