gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma

Douglas J. Schwartzentruber, David H. Lawson, Jon M. Richards, Robert M. Conry, Donald M. Miller, Jonathan Treisman, Fawaz Gailani, Lee Riley, Kevin Conlon, Barbara Pockaj, Kari L. Kendra, Richard L. White, Rene Gonzalez, Timothy M. Kuzel, Brendan Curti, Phillip D. Leming, Eric D. Whitman, Jai Balkissoon, Douglas S. Reintgen, Howard KaufmanFrancesco M. Marincola, Maria J. Merino, Steven A. Rosenberg, Peter Choyke, Don Vena, Patrick Hwu

Research output: Contribution to journalArticle

618 Scopus citations

Abstract

BACKGROUND: Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. METHODS: We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA*A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209-217(210M) plus incomplete Freund's adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end point was clinical response. Secondary end points included toxic effects and progression-free survival. RESULTS: The treatment groups were well balanced with respect to baseline characteristics and received a similar amount of interleukin-2 per cycle. The toxic effects were consistent with those expected with interleukin-2 therapy. The vaccine-interleukin-2 group, as compared with the interleukin-2-only group, had a significant improvement in centrally verified overall clinical response (16% vs. 6%, P = 0.03), as well as longer progression-free survival (2.2 months; 95% confidence interval [CI], 1.7 to 3.9 vs. 1.6 months; 95% CI, 1.5 to 1.8; P = 0.008). The median overall survival was also longer in the vaccine-interleukin-2 group than in the interleukin-2-only group (17.8 months; 95% CI, 11.9 to 25.8 vs. 11.1 months; 95% CI, 8.7 to 16.3; P = 0.06). CONCLUSIONS: In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone.

Original languageEnglish (US)
Pages (from-to)2119-2127
Number of pages9
JournalNew England Journal of Medicine
Volume364
Issue number22
DOIs
StatePublished - Jun 2 2011

ASJC Scopus subject areas

  • Medicine(all)

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    Schwartzentruber, D. J., Lawson, D. H., Richards, J. M., Conry, R. M., Miller, D. M., Treisman, J., Gailani, F., Riley, L., Conlon, K., Pockaj, B., Kendra, K. L., White, R. L., Gonzalez, R., Kuzel, T. M., Curti, B., Leming, P. D., Whitman, E. D., Balkissoon, J., Reintgen, D. S., ... Hwu, P. (2011). gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. New England Journal of Medicine, 364(22), 2119-2127. https://doi.org/10.1056/NEJMoa1012863