Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade.

Journal Article (Journal Article)

PURPOSE: CTL-associated antigen 4 (CTLA-4) can inhibit T-cell activation and helps maintain peripheral self-tolerance. Previously, we showed immune-related adverse events (IRAE) and objective, durable clinical responses in patients with metastatic melanoma treated with CTLA-4 blockade. We have now treated 139 patients in two trials and have sufficient follow-up to examine factors associated with clinical response. EXPERIMENTAL DESIGN: A total of 139 patients with metastatic melanoma were treated: 54 patients received ipilimumab in conjunction with peptide vaccinations and 85 patients were treated with intra-patient dose escalation of ipilimumab and randomized to receive peptides in accordance with HLA-A*0201 status. RESULTS: Three patients achieved complete responses (CR; ongoing at 29+, 52+, and 53+ months); an additional 20 patients achieved partial responses (PR) for an overall objective response rate of 17%. The majority of patients (62%, 86 of 139) developed some form of IRAE, which was associated with a greater probability of objective antitumor response (P = 0.0004); all patients with CR had more severe IRAEs. Prior therapy with IFNalpha-2b was a negative prognostic factor, whereas prior high-dose interleukin-2 did not significantly affect the probability of response. There were no significant differences in the rate of clinical response or development of IRAEs between the two trials. The duration of tumor response was not affected by the use of high-dose steroids for abrogation of treatment-related toxicities (P = 0.23). There were no treatment-related deaths. CONCLUSION: In patients with metastatic melanoma, ipilimumab can induce durable objective clinical responses, which are related to the induction of IRAEs.

Full Text

Duke Authors

Cited Authors

  • Downey, SG; Klapper, JA; Smith, FO; Yang, JC; Sherry, RM; Royal, RE; Kammula, US; Hughes, MS; Allen, TE; Levy, CL; Yellin, M; Nichol, G; White, DE; Steinberg, SM; Rosenberg, SA

Published Date

  • November 15, 2007

Published In

Volume / Issue

  • 13 / 22 Pt 1

Start / End Page

  • 6681 - 6688

PubMed ID

  • 17982122

Pubmed Central ID

  • PMC2147083

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-07-0187

Language

  • eng

Conference Location

  • United States