Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4

Peter Attia, Giao Q. Phan, Ajay V. Maker, Michael R. Robinson, Martha M. Quezado, James C. Yang, Richard M. Sherry, Suzanne L. Topalian, Udai S. Kammula, Richard E. Royal, Nicholas P. Restifo, Leah R. Haworth, Catherine Levy, Sharon A. Mavroukakis, Geoff Nichol, Michael J. Yellin, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

Purpose: Previously, we reported our experience treating 14 patients with metastatic melanoma using a fully human antibody to cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) in conjunction with peptide vaccination. We have now treated 56 patients to evaluate two different dose schedules of anti-CTLA-4 and to explore the relationship between autoimmunity and tumor regression. Patients and Methods: A total of 56 patients with progressive stage IV melanoma were enrolled onto the study. All had Karnofsky performance status ≥ 60% with no prior history of autoimmunity. Twenty-nine patients received 3 mg/kg anti-CTLA-4 every 3 weeks, whereas 27 received 3 mg/kg as their initial dose with subsequent doses reduced to 1 mg/kg every 3 weeks. In both cohorts patients received concomitant vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-288(288V). Results: Two patients achieved a complete response (ongoing at 30 and 31 months, respectively) and five patients achieved a partial response (durations of 4, 6, 25+, 26+, and 34+ months, respectively), for an overall objective response rate of 13%. Tumor regression was seen in lung, liver, brain, lymph nodes, and subcutaneous sites. Of 14 patients with grade 3/4 autoimmune toxicity, five (36%) experienced a clinical response compared with only two responses in the 42 patients (5%) with no autoimmune toxicity (P = .008). There were no significant differences in response rate or toxicity between the two dose schedules. Conclusion: Administration of anti-CTLA-4 monoclonal antibody plus peptide vaccination can cause durable objective responses, which correlate with the induction of autoimmunity, in patients with metastatic melanoma.

Original languageEnglish (US)
Pages (from-to)6043-6053
Number of pages11
JournalJournal of Clinical Oncology
Volume23
Issue number25
DOIs
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Attia, P., Phan, G. Q., Maker, A. V., Robinson, M. R., Quezado, M. M., Yang, J. C., Sherry, R. M., Topalian, S. L., Kammula, U. S., Royal, R. E., Restifo, N. P., Haworth, L. R., Levy, C., Mavroukakis, S. A., Nichol, G., Yellin, M. J., & Rosenberg, S. A. (2005). Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. Journal of Clinical Oncology, 23(25), 6043-6053. https://doi.org/10.1200/JCO.2005.06.205