gp100 Peptide Vaccine and Interleukin-2 in Patients with Advanced Melanoma

By D. Schwartzentruber, D. Lawson, J. Richards, R. Conry, Donald M Miller, J. Treisman, F. Gailani, L. Riley, K. Conlon, B. Pockaj and 16 more. New England Journal of Medicine, 2011

808 citations recorded by the source corpus.

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. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00019682.)

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/3ed32310df46c82acf66015e3dc5c8937a28cc5f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Sylvia M. Lee
2. S. Farkona
3. Eleftherios P. Diamandis
4. K. Margolin
5. I. Blasutig

In Molecular Biology

1. Eleftherios P. Diamandis
2. Andrew Emili
3. Jennifer Listgarten

In Oncology

1. Sylvia M. Lee
2. S. Farkona
3. Eleftherios P. Diamandis
4. K. Margolin
5. I. Blasutig

Citations in the corpus

• Cytokines in Cancer Immunotherapy (2011, background): “The initial results have been mixed [199-201], and current therapies that appear to have a superior therapeutic index and to be more widely available (not requiring a specific HLA type as peptide vaccines do) are”
• Cancer immunotherapy: the beginning of the end of cancer? (2016, background): “As it was later shown, the therapeutic efficacy of cancer vaccines can be improved when immune stimulants such as IL-2 are co-administered with short peptide vaccines [12].”
• Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. (2015, neutral): “Analyses of immune responses during anti-PD therapy indicate that selective expansion and functional enhancement of T cells occur at the tumor site, while activity of immune cells in the bloodstream fails to correlate with tumor regression (78–80).”
• Interleukin-2 at the Crossroads of Effector Responses, Tolerance, and Immunotherapy (2013, neutral): “Vaccination with a melanoma peptide vaccine can significantly improve effectiveness (Schwartzentruber et al., 2011), and the addition of adoptive cell transfer 20 Immunity 38, January 24, 2013 ª2013 Elsevier Inc. approaches have improved cure rates for metastatic melanoma to between 20% and 40%…”
• Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry (2016, neutral): “A 4-tiered system was used for scoring: (0) absent, (1) 40–25%, (2) 425–50%, (3) 450–75%, (4) 475–100%.”
• Therapeutic cancer vaccines. (2010, result): “Survival advantage was also noted in a study of an HLA-A2–binding gp100-derived short peptide vaccine together with IL-2, versus treatment with IL-2 alone in patients with advanced melanoma (34).”