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

Publication ,  Journal Article
Downey, SG; Klapper, JA; Smith, FO; Yang, JC; Sherry, RM; Royal, RE; Kammula, US; Hughes, MS; Allen, TE; Levy, CL; Yellin, M; Nichol, G ...
Published in: Clin Cancer Res
November 15, 2007

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.

Duke Scholars

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Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

November 15, 2007

Volume

13

Issue

22 Pt 1

Start / End Page

6681 / 6688

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Skin Neoplasms
  • Prognosis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Melanoma
  • Male
  • Ipilimumab
  • Humans
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Downey, S. G., Klapper, J. A., Smith, F. O., Yang, J. C., Sherry, R. M., Royal, R. E., … Rosenberg, S. A. (2007). Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin Cancer Res, 13(22 Pt 1), 6681–6688. https://doi.org/10.1158/1078-0432.CCR-07-0187
Downey, Stephanie G., Jacob A. Klapper, Franz O. Smith, James C. Yang, Richard M. Sherry, Richard E. Royal, Udai S. Kammula, et al. “Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade.Clin Cancer Res 13, no. 22 Pt 1 (November 15, 2007): 6681–88. https://doi.org/10.1158/1078-0432.CCR-07-0187.
Downey SG, Klapper JA, Smith FO, Yang JC, Sherry RM, Royal RE, et al. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6681–8.
Downey, Stephanie G., et al. “Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade.Clin Cancer Res, vol. 13, no. 22 Pt 1, Nov. 2007, pp. 6681–88. Pubmed, doi:10.1158/1078-0432.CCR-07-0187.
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. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6681–6688.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

November 15, 2007

Volume

13

Issue

22 Pt 1

Start / End Page

6681 / 6688

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Skin Neoplasms
  • Prognosis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Melanoma
  • Male
  • Ipilimumab
  • Humans
  • Female