Interleukin-2 and experimental immunotherapy approaches for advanced melanoma
- Jeffrey A Sosman, MD
Jeffrey A Sosman, MD
- Professor of Medicine
- Robert H. Lurie Comprehensive Cancer Center of Northwestern
Although the incidence of malignant melanoma is increasing, most cases are diagnosed at an early stage. For localized melanomas, surgical excision is curative in most cases, and patients at high risk of developing metastatic disease may benefit from adjuvant therapy. (See "Initial surgical management of melanoma of the skin and unusual sites" and "Adjuvant immunotherapy for melanoma".)
High-dose interleukin-2 (IL-2) was the first immunotherapy approach to produce durable remissions in patients with advanced disease. However, these benefits were limited to a small fraction of patients, and treatment was associated with substantial toxicity.
The use of high-dose IL-2 in melanoma has largely been replaced by immunotherapy with checkpoint inhibitors directed against programmed death-1 protein (PD-1) alone or in combination with antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4). In addition, targeted therapy directed against the mitogen-activated protein (MAP) kinase pathway has provided an additional important treatment option for patients with advanced disease and a V600 mutation of BRAF.
The results with high-dose IL-2 and the potential role of other experimental immunotherapy approaches are reviewed here.
The principles of cancer immunotherapy and an overview of the treatment of metastatic melanoma are presented separately:
- Rosenberg SA, Mulé JJ, Spiess PJ, et al. Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin 2. J Exp Med 1985; 161:1169.
- Rosenberg SA, Yang JC, Topalian SL, et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 1994; 271:907.
- Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999; 17:2105.
- Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am 2000; 6 Suppl 1:S11.
- Rosenberg SA, Lotze MT, Muul LM, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 1987; 316:889.
- Schwartzentruber DJ, Lawson DH, Richards JM, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med 2011; 364:2119.
- O'Day SJ, Atkins MB, Boasberg P, et al. Phase II multicenter trial of maintenance biotherapy after induction concurrent Biochemotherapy for patients with metastatic melanoma. J Clin Oncol 2009; 27:6207.
- Atkins MB, Hsu J, Lee S, et al. Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b with cisplatin, vinblastine, and dacarbazine alone in patients with metastatic malignant melanoma (E3695): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2008; 26:5748.
- Bernatchez C, Haymaker C, Tannier NM, et al. A CD122-biased agonist increases CD8+ T cells and natural killer cells in the tumor microenvironment; making cold tumors hot with NKTR-214 (abstract). Society for Immunotherapy of Cancer 2016 meeting.
- Rosenberg SA, Yannelli JR, Yang JC, et al. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst 1994; 86:1159.
- Rosenberg SA, Yang JC, Sherry RM, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 2011; 17:4550.
- Dummer R, Garbe C, Thompson JA, et al. Randomized dose-escalation study evaluating peginterferon alfa-2a in patients with metastatic malignant melanoma. J Clin Oncol 2006; 24:1188.
- Agarwala SS, Kirkwood JM. Interferons in melanoma. Curr Opin Oncol 1996; 8:167.
- Creagan ET, Ahmann DL, Frytak S, et al. Phase II trials of recombinant leukocyte A interferon in disseminated malignant melanoma: results in 96 patients. Cancer Treat Rep 1986; 70:619.
- Agarwala SS, Kirkwood JM. Adjuvant interferon treatment for melanoma. Hematol Oncol Clin North Am 1998; 12:823.
- Nawrocki S, Murawa P, Malicki J, et al. Genetically modified tumour vaccines (GMTV) in melanoma clinical trials. Immunol Lett 2000; 74:81.
- Szabolcs P, Moore MA, Young JW. Expansion of immunostimulatory dendritic cells among the myeloid progeny of human CD34+ bone marrow precursors cultured with c-kit ligand, granulocyte-macrophage colony-stimulating factor, and TNF-alpha. J Immunol 1995; 154:5851.
- Lawson DH, Lee SJ, Tarhini AA, et al. Phase III cooperative group study of yeast-derived granulocyte macrophage colony stimulating factor (GM-CSF) versus placebo as adjuvant treatment of patients with completely resected stage III_IV melanoma. J Clin Oncol 2010; 28:612s.
- Hodi FS, Lee S, McDermott DF, et al. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA 2014; 312:1744.