Advances in immunotherapy for melanoma

BMC Medicine

Volumn 14, Issue 1, 2016, Pages

  Redman, Jason M ^a,b   Gibney, Geoffrey T ^a,b   Atkins, Michael B ^a,b  

^a GEORGETOWN UNIVERSITY   (United States)

^b GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Anti PD 1; Immunotherapy; Ipilimumab; Melanoma; Nivolumab; Pembrolizumab

Indexed keywords

ANTINEOPLASTIC AGENT; ATEZOLIZUMAB; BIOLOGICAL MARKER; CD27 ANTIGEN; DACARBAZINE; DURVALUMAB; EPACADOSTAT; INTERFERON; IPILIMUMAB; MEDI 6883; NIVOLUMAB; PEGINTERFERON; PEMBROLIZUMAB; PF 05082566; PLACEBO; PROGRAMMED DEATH 1 RECEPTOR; SARGRAMOSTIM; TALIMOGENE LAHERPAREPVEC; TICILIMUMAB; UNCLASSIFIED DRUG; VARILILUMAB; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; MONOCLONAL ANTIBODY;

ANTIGEN EXPRESSION; ARTHRALGIA; BRAIN EDEMA; BRAIN HEMORRHAGE; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER STAGING; CANCER SURVIVAL; COLITIS; DERMATITIS; DIARRHEA; DIZZINESS; DRUG APPROVAL; DRUG EFFICACY; DRUG MEGADOSE; DRUG RESPONSE; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; HEADACHE; HEPATITIS; HUMAN; HYPERGLYCEMIA; HYPERTRANSAMINASEMIA; HYPOPHYSITIS; HYPOTHYROIDISM; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; IMMUNOSTIMULATION; LONG TERM SURVIVAL; LOW DRUG DOSE; MELANOMA; METASTATIC MELANOMA; NAUSEA; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHASE 4 CLINICAL TRIAL (TOPIC); PNEUMONIA; PROGRESSION FREE SURVIVAL; PRURITUS; RASH; RECURRENCE FREE SURVIVAL; SHORT SURVEY; SURVIVAL RATE; THYROIDITIS; TREATMENT DURATION; TREATMENT OUTCOME; ANTAGONISTS AND INHIBITORS; CONTRAINDICATIONS; DISEASE FREE SURVIVAL; IMMUNOLOGY; IMMUNOTHERAPY; MULTIMODALITY CANCER THERAPY; PATHOLOGY; PROCEDURES;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; COMBINED MODALITY THERAPY; CTLA-4 ANTIGEN; DISEASE-FREE SURVIVAL; HUMANS; IMMUNOTHERAPY; MELANOMA; PROGRAMMED CELL DEATH 1 RECEPTOR;

EID: 84957097035     PISSN: None     EISSN: 17417015     Source Type: Journal    
DOI: 10.1186/s12916-016-0571-0     Document Type: Short Survey

References (85)

1. Garbe C, Eigentler TK, Keilholz U, Hauschild A, Kirkwood JM. Systematic review of medical treatment in melanoma: current status and future prospects. Oncologist. 2011;16:5-24.
2. Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, 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.
3. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985;313:1485-92.
4. Pastorfide GC, Kibbi AG, de Roa AL, Barnhill RL, Sober AJ, Mihm Jr MC, et al. Image analysis of stage 1 melanoma (1.00-2.50 mm): lymphocytic infiltrates related to metastasis and survival. J Cutan Pathol. 1992;19:390-7.
5. Sober AJ, Day Jr CL, Fitzpatrick TB, Lew RA, Kopf AW, Mihm Jr MC. Factors associated with death from melanoma from 2 to 5 years following diagnosis in clinical stage I patients. J Invest Dermatol. 1983;80 Suppl:53s-5s.
6. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, 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.
7. Harlin H, Kuna TV, Peterson AC, Meng Y, Gajewski TF. Tumor progression despite massive influx of activated CD8(+) T cells in a patient with malignant melanoma ascites. Cancer Immunol Immunother. 2006;55:1185-97.
8. Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, et al. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med. 2013;5:200ra116.
9. Strome SE, Dong H, Tamura H, Voss SG, Flies DB, Tamada K, et al. B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res. 2003;63:6501-5.
10. Wong RM, Scotland RR, Lau RL, Wang C, Korman AJ, Kast WM, et al. Programmed death-1 blockade enhances expansion and functional capacity of human melanoma antigen-specific CTLs. Int Immunol. 2007;19:1223-34.
11. Yao S, Zhu Y, Chen L. Advances in targeting cell surface signalling molecules for immune modulation. Nat Rev Drug Discov. 2013;12:130-46.
12. Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322:271-5.
13. Peggs KS, Quezada SA, Chambers CA, Korman AJ, Allison JP. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med. 2009;206:1717-25.
14. Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A. 2003;100:8372-7.
15. Attia P, Phan GQ, Maker AV, Robinson MR, Quezado MM, Yang JC, et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol. 2005;23:6043-53.
16. Maker AV, Yang JC, Sherry RM, Topalian SL, Kammula US, Royal RE, et al. Intrapatient dose escalation of anti-CTLA-4 antibody in patients with metastatic melanoma. J Immunother. 2006;29:455-63.
17. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711-23.
18. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517-26.
19. Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol. 2015;33:1889-4.
20. Camacho LH, Antonia S, Sosman J, Kirkwood JM, Gajewski TF, Redman B, et al. Phase I/II trial of tremelimumab in patients with metastatic melanoma. J Clin Oncol. 2009;27:1075-81.
21. Ribas A, Kefford R, Marshall MA, Punt CJ, Haanen JB, Marmol M, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol. 2013;31:616-22.
22. Bertrand A, Kostine M, Barnetche T, Truchetet ME, Schaeverbeke T. Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis. BMC Med. 2015;13:211.
23. Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30:2691-7.
24. Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15:7412-20.
25. Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28:3167-75.
26. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443-54.
27. Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32:1020-30.
28. Hodi FS, Sznol M, Kluger HM, McDermott DF, Carvajal RD, Lawrence DP, et al. Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial. J Clin Oncol. 2014;32:5s. suppl; abstr 9002.
29. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369:134-44.
30. Daud A, Ribas A, Robert C, Hodi FS, Wolchok JD, Joshua AM, et al. Long-term efficacy of pembrolizumab (pembro; MK-3475) in a pooled analysis of 655 patients (pts) with advanced melanoma (MEL) enrolled in KEYNOTE-001. J Clin Oncol. 2015;33:(suppl; abstr 9005).
31. Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16:375-84.
32. Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16:908-18.
33. Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, 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.
34. Lutzky J, Antonia SJ, Blake-Haskins A, Li X, Robbins PB, Shalabi AM, et al. A phase 1 study of MEDI4736, an anti-PD-L1 antibody, in patients with advanced solid tumors. J Clin Oncol. 2014;32(5s):(suppl; abstr 3001^).
35. Hamid O, Sosman JA, Lawrence DP, Sullivan RJ, Ibrahim N, Kluger HM, et al. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM). J Clin Oncol. 2013;31:(suppl; abstr 9010).
36. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521-32.
37. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23-34.
38. Gibney GT, Atkins MB. Swinging for the fences: long-term survival with ipilimumab in metastatic melanoma. J Clin Oncol. 2015;33:1873-7.
39. Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13:459-65.
40. Kluger HM, Zito CR, Barr ML, Baine MK, Chiang VL, Sznol M, et al. Characterization of PD-L1 expression and associated T-cell infiltrates in metastatic melanoma samples from variable anatomic sites. Clin Cancer Res. 2015;21:3052-60.
41. Kluger HM, Goldberg SB, Sznol M, Tsiouris J, Vortmeyer A, Jilaveanu L, et al. Safety and activity of pembrolizumab in melanoma patients with untreated brain metastases. J Clin Oncol. 2015;33:(suppl; abstr 9009).
42. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27:6199-206.
43. Kirkwood JM, Manola J, Ibrahim J, Sondak V, Ernstoff MS, Rao U. A pooled analysis of eastern cooperative oncology group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res. 2004;10:1670-7.
44. Eggermont AM, Suciu S, Testori A, Santinami M, Kruit WH, Marsden J, et al. Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma. J Clin Oncol. 2012;30:3810-8.
45. Tarhini AA, Thalanayar PM. Melanoma adjuvant therapy. Hematol Oncol Clin North Am. 2014;28:471-89.
46. Flaherty LE, Othus M, Atkins MB, Tuthill RJ, Thompson JA, Vetto JT, et al. Southwest Oncology Group S0008: a phase III trial of high-dose interferon Alfa-2b versus cisplatin, vinblastine, and dacarbazine, plus interleukin-2 and interferon in patients with high-risk melanoma--an intergroup study of cancer and leukemia Group B, Children's Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. J Clin Oncol. 2014;32:3771-8.
47. Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16:522-30.
48. Tarhini AA. Adjuvant Therapy for High-Risk Melanoma. Am J Hematol Oncol. 2014;10:4-13.
49. Gibney GT, Kudchadkar RR, DeConti RC, Thebeau MS, Czupryn MP, Tetteh L, et al. Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma. Clin Cancer Res. 2015;21:712-20.
50. Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. 2010;107:4275-80.
51. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369:122-33.
52. Sznol M, Kluger HM, Callahan MK, Postow MA, Gordon RA, Segal NH, et al. Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). J Clin Oncol. 2014;32(5s):(suppl; abstr LBA9003^).
53. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372:2006-17.
54. Hodi FS, Gibney GT, Sullivan R, Sosman JA, Slingluff CL, Lawrence DP, et al. An open-label, randomized, phase 2 study of nivolumab given sequentially with ipilimumab in patients with advanced melanoma (Checkmate 064). ECCO-ESMO. 25-29 September 2015. 2015:abstract 23LBA.
55. Atkins MB, Choueiri TK, Hodi FS, Thompson JA, Hwu W, McDermott DF, et al. Pembrolizumab (MK-3475) plus low-dose ipilimumab (IPI) in patients (pts) with advanced melanoma (MEL) or renal cell carcinoma (RCC): Data from the KEYNOTE-029 phase 1 study. J Clin Oncol. 2015;33(5s):(suppl; abstr 3009).
56. Kudchadkar RR, Gibney GT, Dorman D, Merek S, Ramadan H, Chen A, et al. A phase IB study of ipilimumab with peginterferon alfa-2b for patients with unresectable stages IIIB/C/IV melanoma. J Clin Oncol. 2014;32(5s):(suppl; abstr 9098).
57. Hodi FS, Lee S, McDermott DF, Rao UN, Butterfield LH, Tarhini AA, et al. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA. 2014;312:1744-53.
58. Zarour HM, Tawbi H, Tarhini AA, Wang H, Sander C, Rose A, et al. Study of anti-PD-1 antibody pembrolizumab and pegylated-interferon alfa-2b (Peg-IFN) for advanced melanoma. J Clin Oncol. 2015;33:(suppl; abstr e20018).
59. Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33:2780-8.
60. Puzanov I, Milhem MM, Andtbacka RHI, Minor DR, Hamid O, Li A, et al. Survival, safety, and response patterns in a phase 1b multicenter trial of talimogene laherparepvec (T-VEC) and ipilimumab (IPI) in previously untreated, unresected stage IIIB-IV melanoma. J Clin Oncol. 2015;33:(suppl; abstr 9063).
61. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003;9:1269-74.
62. Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010;115:3520-30.
63. Beatty GL DP, Clark J, Shi JG, Newton RC, Schaub R, Maleski J, et al. Phase I study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the oral inhibitor of indoleamine 2,3-dioxygenase (IDO1) INCB024360 in patients (pts) with advanced malignancies. J Clin Oncol 31, 2013 (suppl; abstr 3025). http://meetinglibrary.asco.org/content/115661-132. Accessed 21 Nov 2015.
64. Gibney GT, Hamid O, Lutzky J, Olszanski AJ, Gangadhar TC, Gajewski TF, et al. Updated results from a phase 1/2 study of epacadostat (INCB024360) in combination with ipilimumab in patients with metastatic melanoma. ECCO-ESMO 2015: abstract 511. 2015. http://www.europeancancercongress.org/Scientific-Programme/Abstract-search?abstractid=23278. Accessed 22 Jan 2016.
65. Spranger S, Koblish HK, Horton B, Scherle PA, Newton R, Gajewski TF. Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment. J Immunother Cancer. 2014;2:3.
66. Gangadhar TC, Hamid O, Smith DC, Bauer TM, Wasser JS, Luke JJ, et al. Preliminary results from a Phase I/II study of epacadostat (incb024360) in combination with pembrolizumab in patients with selected advanced cancers. J Immunother Cancer. 2015;3 Suppl 2:O7.
67. Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012;72:917-27.
68. Okazaki T, Okazaki IM, Wang J, Sugiura D, Nakaki F, Yoshida T, et al. PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice. J Exp Med. 2011;208:395-407.
69. Taube JM, Young GD, McMiller TL, Chen S, Salas JT, Pritchard TS, et al. Differential expression of immune-regulatory genes associated with PD-L1 display in melanoma: implications for PD-1 pathway blockade. Clin Cancer Res. 2015;21:3969-76.
70. Sabatino M, Kim-Schulze S, Panelli MC, Stroncek D, Wang E, Taback B, et al. Serum vascular endothelial growth factor and fibronectin predict clinical response to high-dose interleukin-2 therapy. J Clin Oncol. 2009;27:2645-52.
71. Panelli MC, Wang E, Phan G, Puhlmann M, Miller L, Ohnmacht GA, et al. Gene-expression profiling of the response of peripheral blood mononuclear cells and melanoma metastases to systemic IL-2 administration. Genome Biol. 2002;3(7):RESEARCH0035.
72. Mahoney KM, Atkins MB. Prognostic and predictive markers for the new immunotherapies. Oncology (Williston Park). 2014;28 Suppl 3:39-48.
73. Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14:847-56.
74. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018-28.
75. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627-39.
76. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568-71.
77. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;4:127ra137.
78. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20:5064-74.
79. Ribas A, Robert C, Hodi FS, Wolchok JD, Joshua AM, Hwu W-J, et al. Association of response to programmed death receptor 1 (PD-1) blockade with pembrolizumab (MK-3475) with an interferon-inflammatory immune gene signature. J Clin Oncol. 2015;33:(suppl; abstr 3001).
80. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371:2189-99.
81. Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015;350:207-11.
82. Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell. 2015;160:48-61.
83. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124-8.
84. F Freeman-Keller ML, Weber JS. Nivolumab in resected and unresectable melanoma: Immune-related adverse events and association with survival outcomes. J Clin Oncol. 2015;33:(suppl; abstr 9028).
85. Horvat TZ, Adel NG, Dang TO, Momtaz P, Postow MA, Callahan MK, et al. Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at Memorial Sloan Kettering Cancer Center. J Clin Oncol. 2015;33:3193-8.