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

Stephanie G. Downey, Jacob A. Klapper, Franz O. Smith, James C. Yang, Richard M. Sherry, Richard E. Royal, Udai S. Kammula, Marybeth S. Hughes, Tamika E. Allen, Catherine L. Levy, Michael Yellin, Geoffrey Nichol, Donald E. White, Seth M. Steinberg, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

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 IFNα-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.

Original languageEnglish (US)
Pages (from-to)6681-6688
Number of pages8
JournalClinical Cancer Research
Volume13
Issue number22
DOIs
StatePublished - Nov 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Downey, S. G., Klapper, J. A., Smith, F. O., Yang, J. C., Sherry, R. M., Royal, R. E., Kammula, U. S., Hughes, M. S., Allen, T. E., Levy, C. L., Yellin, M., Nichol, G., White, D. E., Steinberg, S. M., & Rosenberg, S. A. (2007). Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clinical Cancer Research, 13(22), 6681-6688. https://doi.org/10.1158/1078-0432.CCR-07-0187