Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy

References

• Smith FO, Downey SG, Klapper JA, Yang JC, Sherry RM, Royal RE, Kammula US, Hughes MS, Restifo NP, Levy CL, et al. Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin Cancer Res 2008; 14:5610–8; PMID:18765555; http://dx.doi.org/10.1158/1078-0432.CCR-08-0116
   PubMed Web of Science ®Google Scholar
• Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, 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; 17:2105–16; PMID:10561265
   PubMed Web of Science ®Google Scholar
• Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363:711–23; PMID:20525992; http://dx.doi.org/10.1056/NEJMoa1003466
   PubMed Web of Science ®Google Scholar
• Chow S, Cove-Smith L, Schmitt M, Hawkins R. High-dose interleukin 2-induced myocarditis: can myocardial damage reversibility be assessed by cardiac MRI? J Immunother 2014; 37:304–8; PMID:24810642; http://dx.doi.org/10.1097/CJI.0000000000000036
   PubMed Web of Science ®Google Scholar
• Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, Lee RJ, Grippo JF, Nolop K, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010; 363:809–19; PMID:20818844; http://dx.doi.org/10.1056/NEJMoa1002011
   PubMed Web of Science ®Google Scholar
• Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364:2507–16; PMID:21639808; http://dx.doi.org/10.1056/NEJMoa1103782
   PubMed Web of Science ®Google Scholar
• Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 2000; 18:158–66; PMID:10623706
   PubMed Web of Science ®Google Scholar
• Kottschade LA, Suman VJ, Amatruda T.3rd, McWilliams RR, Mattar BI, Nikcevich DA, Behrens R, Fitch TR, Jaslowski AJ, Markovic SN, et al. A phase II trial of nab-paclitaxel (ABI-007) and carboplatin in patients with unresectable stage IV melanoma : a North Central Cancer Treatment Group Study, N057E(1). Cancer 2011; 117:1704–10; PMID:21472717; http://dx.doi.org/10.1002/cncr.25659
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network: Melanoma ( Version 3.2014). http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf. Accessed April 19, 2014
   Google Scholar
• Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011; 364:2517–26; PMID:21639810; http://dx.doi.org/10.1056/NEJMoa1104621
   PubMed Web of Science ®Google Scholar
• Ribas A, Hodi FS, Callahan M, Konto C, Wolchok J. Hepatotoxicity with combination of vemurafenib and ipilimumab. New Eng J Med 2013; 368:1365–6; PMID:23550685; http://dx.doi.org/10.1056/NEJMc1302338
   PubMed Web of Science ®Google Scholar
• Fateh S, Schell TD, Gingrich R, Neves RI, Drabick JJ. Unsuccessful high dose IL-2 therapy followed immediately by near continuous low dose temozolomide can result in rapid durable complete and near-complete remissions in metastatic melanoma. Cancer Biol Ther 2010; 10:1091–7; PMID:20930514; http://dx.doi.org/10.4161/cbt.10.11.13452
   PubMed Web of Science ®Google Scholar
• High Dose Interleukin-2 Followed by Intermittent Low Dose Temozolomide in Patients With Melanoma”: NCT 01124734. (Accessed at http://clinicaltrials.gov/ct2/show/NCT01124734.)
   Google Scholar
• Hiniker SM, Chen DS, Reddy S, Chang DT, Jones JC, Mollick JA, Swetter SM, Knox SJ. A systemic complete response of metastatic melanoma to local radiation and immunotherapy. Transl Oncol 2012; 5:404–7; PMID:23323154; http://dx.doi.org/10.1593/tlo.12280
   PubMed Web of Science ®Google Scholar
• Barker CA, Postow MA. Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes. Int J Radiat Oncol Biol Phys 2014; 88:986–97; PMID:24661650; http://dx.doi.org/10.1016/j.ijrobp.2013.08.035
   PubMed Web of Science ®Google Scholar
• Das Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, Dummer R, McMahon M, Stuart D. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature 2013; 494:251–5; PMID:23302800; http://dx.doi.org/10.1038/nature11814
   PubMed Web of Science ®Google Scholar
• Ahmadzadeh M, Rosenberg SA. IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients. Blood 2006; 107:2409–14; PMID:16304057; http://dx.doi.org/10.1182/blood-2005-06-2399
   PubMed Web of Science ®Google Scholar
• Cesana GC, DeRaffele G, Cohen S, Moroziewicz D, Mitcham J, Stoutenburg J, Cheung K, Hesdorffer C, Kim-Schulze S, Kaufman HL. Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J Clin Oncol 2006; 24:1169–77; PMID:16505437; http://dx.doi.org/10.1200/JCO.2005.03.6830
   PubMed Web of Science ®Google Scholar
• Wei S, Kryczek I, Edwards RP, Zou L, Szeliga W, Banerjee M, Cost M, Cheng P, Chang A, Redman B, et al. Interleukin-2 administration alters the CD4+FOXP3+ T-cell pool and tumor trafficking in patients with ovarian carcinoma. Cancer Res 2007; 67:7487–94; PMID:17671219; http://dx.doi.org/10.1158/0008-5472.CAN-07-0565
   PubMed Web of Science ®Google Scholar
• Gogas H, Polyzos A, Kirkwood J. Immunotherapy for advanced melanoma: fulfilling the promise. Cancer Treat Rev 2013; 39:879–85; PMID:23725878; http://dx.doi.org/10.1016/j.ctrv.2013.04.006
   PubMed Web of Science ®Google Scholar
• 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:S11–4; PMID:10685652
   PubMed Web of Science ®Google Scholar
• Bhatia S, Tykodi SS, Thompson JA. Treatment of metastatic melanoma: an overview. Oncology (Williston Park) 2009; 23:488–96; PMID:19544689
   PubMed Web of Science ®Google Scholar
• Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, Weber JS, Joshua AM, Hwu WJ, Gangadhar TC, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 2014; 384:1109–17; PMID:25034862; http://dx.doi.org/10.1016/S0140-6736(14)60958-2
   PubMed Web of Science ®Google Scholar
• Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013; 369:122–33; PMID:23724867; http://dx.doi.org/10.1056/NEJMoa1302369
   PubMed Web of Science ®Google Scholar
• Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366:2443–54; PMID:22658127; http://dx.doi.org/10.1056/NEJMoa1200690
   PubMed Web of Science ®Google Scholar
• Hu-Lieskovan S, Robert L, Homet Moreno B, Ribas A. Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges. J Clin Oncol 2014; 32:2248–54; PMID:24958825; http://dx.doi.org/10.1200/JCO.2013.52.1377
   PubMed Web of Science ®Google Scholar
• Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 2012; 12:237–51; PMID:22437869; http://dx.doi.org/10.1038/nrc3237
   PubMed Web of Science ®Google Scholar
• Homet B, Ribas A. New drug targets in metastatic melanoma. J Pathol 2014; 232:134–41; PMID:24027077; http://dx.doi.org/10.1002/path.4259
   PubMed Web of Science ®Google Scholar
• Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 2012; 366:707–14; PMID:22356324; http://dx.doi.org/10.1056/NEJMoa1112302
   PubMed Web of Science ®Google Scholar
• Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH Jr, Kaempgen E, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012; 380:358–65; PMID:22735384; http://dx.doi.org/10.1016/S0140-6736(12)60868-X
   PubMed Web of Science ®Google Scholar
• Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 2014; 371:1877–88; PMID:25265492; http://dx.doi.org/10.1056/NEJMoa1406037
   PubMed Web of Science ®Google Scholar
• Johnson DB, Flaherty KT, Weber JS, Infante JR, Kim KB, Kefford RF, Hamid O, Schuchter L, Cebon J, Sharfman WH, et al. Combined BRAF (Dabrafenib) and MEK Inhibition (Trametinib) in Patients With BRAFV600-Mutant Melanoma Experiencing Progression With Single-Agent BRAF Inhibitor. J Clin Oncol 2014; 32:3697–704; PMID:25287827; http://dx.doi.org/10.1200/JCO.2014.57.3535
   PubMed Web of Science ®Google Scholar
• Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, Demidov LV, Hassel JC, Rutkowski P, Mohr P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012; 367:107–14; PMID:22663011; http://dx.doi.org/10.1056/NEJMoa1203421
   PubMed Web of Science ®Google Scholar
• Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbé C, Maio M, Binder M, Bohnsack O, Nichol G, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15:7412–20; PMID:19934295; http://dx.doi.org/10.1158/1078-0432.CCR-09-1624
   PubMed Web of Science ®Google Scholar
• Nowak AK, Robinson BW, Lake RA. Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res 2003; 63:4490–6; PMID:12907622
   PubMed Web of Science ®Google Scholar
• Ramakrishnan R, Assudani D, Nagaraj S, Hunter T, Cho HI, Antonia S, Altiok S, Celis E, Gabrilovich DI. Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice. J Clin Invest 2010; 120:1111–24; PMID:20234093; http://dx.doi.org/10.1172/JCI40269
   PubMed Web of Science ®Google Scholar
• Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013; 31:51–72; PMID:23157435; http://dx.doi.org/10.1146/annurev-immunol-032712-100008
   PubMed Web of Science ®Google Scholar
• Ascierto PA, Marincola FM, Ribas A. Anti-CTLA4 monoclonal antibodies: the past and the future in clinical application. J Transl Med 2011; 9:196; PMID:22077981; http://dx.doi.org/10.1186/1479-5876-9-196
   PubMed Web of Science ®Google Scholar
• Vieweg J, Su Z, Dahm P, Kusmartsev S. Reversal of tumor-mediated immunosuppression. Clin Cancer Res 2007; 13:727s-32s; PMID:17255301; http://dx.doi.org/10.1158/1078-0432.CCR-06-1924
   PubMed Web of Science ®Google Scholar
• Bronte V, Apolloni E, Cabrelle A, Ronca R, Serafini P, Zamboni P, Restifo NP, Zanovello P. Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood 2000; 96:3838–46; PMID:11090068
   PubMed Web of Science ®Google Scholar
• Comin-Anduix B, Chodon T, Sazegar H, Matsunaga D, Mock S, Jalil J, Escuin-Ordinas H, Chmielowski B, Koya RC, Ribas A, et al. The oncogenic BRAF kinase inhibitor PLX4032/RG7204 does not affect the viability or function of human lymphocytes across a wide range of concentrations. Clin Cancer Res 2010; 16:6040–8; PMID:21169256; http://dx.doi.org/10.1158/1078-0432.CCR-10-1911
   PubMed Web of Science ®Google Scholar
• Ho PC, Meeth KM, Tsui YC, Srivastava B, Bosenberg MW, Kaech SM. Immune-based antitumor effects of BRAF inhibitors rely on signaling by CD40L and IFNgamma. Cancer Res 2014; 74:3205–17; PMID:24736544; http://dx.doi.org/10.1158/0008-5472.CAN-13-3461
   PubMed Web of Science ®Google Scholar
• Boni A, Cogdill AP, Dang P, Udayakumar D, Njauw CN, Sloss CM, Ferrone CR, Flaherty KT, Lawrence DP, Fisher DE, et al. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res 2010; 70:5213–9; PMID:20551059; http://dx.doi.org/10.1158/0008-5472.CAN-10-0118
   PubMed Web of Science ®Google Scholar
• Disis ML, Bernhard H, Jaffee EM. Use of tumour-responsive T cells as cancer treatment. Lancet 2009; 373:673–83; PMID:19231634; http://dx.doi.org/10.1016/S0140-6736(09)60404-9
   PubMed Web of Science ®Google Scholar
• Appay V. The physiological role of cytotoxic CD4(+) T-cells: the holy grail? Clin Exp Immunol 2004; 138:10–3; PMID:15373899; http://dx.doi.org/10.1111/j.1365-2249.2004.02605.x
   PubMed Web of Science ®Google Scholar
• Prieto PA, Yang JC, Sherry RM, Hughes MS, Kammula US, White DE, Levy CL, Rosenberg SA, Phan GQ. CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res 2012; 18:2039–47; PMID:22271879; http://dx.doi.org/10.1158/1078-0432.CCR-11-1823
   PubMed Web of Science ®Google Scholar
• Coventry BJ, Ashdown ML, Quinn MA, Markovic SN, Yatomi-Clarke SL, Robinson AP. CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool? J Transl Med 2009; 7:102; PMID:19948067; http://dx.doi.org/10.1186/1479-5876-7-102
   PubMed Web of Science ®Google Scholar
• Kim G, McKee AE, Ning YM, Hazarika M, Theoret M, Johnson JR, Xu QC, Tang S, Sridhara R, Jiang X, et al. FDA Approval Summary: Vemurafenib for Treatment of Unresectable or Metastatic Melanoma with the BRAFV600E Mutation. Clin Cancer Res 2014; 20:4994–5000; PMID:25096067; http://dx.doi.org/10.1158/1078-0432.CCR-14-0776
   PubMed Web of Science ®Google Scholar
• Quezada SA, Simpson TR, Peggs KS, Merghoub T, Vider J, Fan X, Blasberg R, Yagita H, Muranski P, Antony PA, et al. Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J Exp Med 2010; 207:637–50; PMID:20156971; http://dx.doi.org/10.1084/jem.20091918
   PubMed Web of Science ®Google Scholar
• Kaufman HL, Wolchok JD. Is tumor immunity the same thing as autoimmunity? Implications for cancer immunotherapy. J Clin Oncol 2006; 24:2230–2; PMID:16710020; http://dx.doi.org/10.1200/JCO.2006.05.6952
   PubMed Web of Science ®Google Scholar