Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma

Clinical Cancer Research

Volumn 21, Issue 4, 2015, Pages 712-720

  Gibney, Geoffrey T ^a,b   Kudchadkar, Ragini R ^c   DeConti, Ronald C ^a,b   Thebeau, Melissa S ^a   Czupryn, Maria P ^a   Tetteh, Leticia ^a   Eysmans, Cabell ^c   Richards, Allison ^a   Schell, Michael J ^a   Fisher, Kate J ^a   Horak, Christine E ^d   Inzunza, H David ^d   Yu, Bin ^a   Martinez, Alberto J ^a   Younos, Ibrahim ^e,f   Weber, Jeffrey S ^a,b  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF SOUTH FLORIDA   (United States)

^c EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d BRISTOL MYERS SQUIBB   (United States)

^e MENOUFIA UNIVERSITY   (Egypt)

^f SULTAN QABOOS UNIVERSITY   (Oman)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; INTERLEUKIN 2 RECEPTOR ALPHA; NIVOLUMAB; PEPTIDE VACCINE; ANTINEOPLASTIC AGENT; CANCER VACCINE; MONOCLONAL ANTIBODY;

ABDOMINAL PAIN; ADRENAL INSUFFICIENCY; ADULT; AGED; ANEMIA; ANHIDROSIS; ANOREXIA; ARTHRALGIA; ARTICLE; BLOATING; BLURRED VISION; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNIZATION; CANCER STAGING; CD8+ T LYMPHOCYTE; CELL POPULATION; CLINICAL ARTICLE; COGNITIVE DEFECT; COLITIS; CONSTIPATION; COUGHING; DIARRHEA; DISEASE ASSOCIATION; DIZZINESS; DRUG EFFECT; DRUG SAFETY; DRUG TOLERABILITY; DRY EYE; DRY SKIN; DYSGEUSIA; DYSPEPSIA; DYSPNEA; ENTERITIS; ERYTHRODERMA; FATIGUE; FEMALE; FLATULENCE; FLU LIKE SYNDROME; FOLLOW UP; GASTRITIS; GASTROESOPHAGEAL REFLUX; GRANULOMA; HEADACHE; HIGH RISK PATIENT; HUMAN; HYPOKALEMIA; HYPOPHYSITIS; HYPOTHYROIDISM; INFUSION RELATED REACTION; INJECTION SITE DISCOMFORT; LIMB WEAKNESS; LYMPHADENOPATHY; MAINTENANCE THERAPY; MALE; MAXIMUM TOLERATED DOSE; MEMORY DISORDER; METASTATIC MELANOMA; MYALGIA; NAUSEA; NIGHT SWEAT; ORAL MUCOSITIS; OVERALL SURVIVAL; PERIORBITAL EDEMA; PHOTOSENSITIVITY; PNEUMONIA; PROCTITIS; PRURITUS; RASH; RECURRENCE FREE SURVIVAL; SORE THROAT; TREATMENT DURATION; TREATMENT OUTCOME; VERTIGO; VITILIGO; VOMITING; WEIGHT REDUCTION; XEROSTOMIA; ADJUVANT CHEMOTHERAPY; CLINICAL TRIAL; DISEASE FREE SURVIVAL; DOSE RESPONSE; KAPLAN MEIER METHOD; MELANOMA; MIDDLE AGED; MORTALITY; PROCEDURES; SKIN NEOPLASMS;

ADULT; AGED; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CANCER VACCINES; CHEMOTHERAPY, ADJUVANT; DISEASE-FREE SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; MALE; MAXIMUM TOLERATED DOSE; MELANOMA; MIDDLE AGED; SKIN NEOPLASMS;

EID: 84923166043     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-14-2468     Document Type: Article

References (43)

1. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002;8:793-800.
2. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000;192:1027-34.
3. Iwai Y, IshidaM, Tanaka Y, Okazaki T, Honjo T,Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A 2002; 99:12293-7.
4. Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimura M. B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res 2004;10:5094-100.
5. Nomi T, Sho M, Akahori T, Hamada K, Kubo A, Kanehiro H, et al. Clinical significance and therapeutic potential of the programmed death-1 ligand/ programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res 2007;13:2151-7.
6. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, et al. Colocalization of in flammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 2012;4:127ra37.
7. Thompson RH, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, et al. Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A 2004;101:17174-9.
8. Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M, et al. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 2005;65:1089-96.
9. Iwai Y, Terawaki S, Honjo T. PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int Immunol 2005;17:133-44.
10. Brahmer JR, Tykodi SS, ChowLQ,HwuWJ, Topalian SL,HwuP, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366:2455-65.
11. 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.
12. Kefford R, Ribas A, Hamid O, Robert C, Daud A, Wolchock JD, et al. Clinical efficacy and correlationwith tumor PD-L1 expression in patients (pts) with melanoma (MEL) treated with the anti-PD-1 monoclonal antibody MK-3475. J Clin Oncol 2014;32:5s:abstr3005.
13. Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimu-mab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 2014;384:1109-17.
14. 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.
15. Weber JS, Kudchadkar RR, Yu B, Gallenstein D, Horak CE, Inzunza HD, et al. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol 2013;31: 4311-8.
16. Hsueh EC, Essner R, Foshag LJ, Ollila DW, Gammon G, O'Day SJ, et al. Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine. J Clin Oncol 2002;20:4549-54.
17. Morton DL, Mozzillo N, Thompson JF, Kelley MC, Faries M, Wagner J, et al. An international, randomized, phase III trial of bacillus Calmette-Guerin (BCG) plus allogeneic melanomavaccine (MCV) or placebo after complete resection of melanoma metastatic to regional or distant sites. J Clin Oncol 2007;25:abstr8508.
18. Sosman JA, Moon J, Tuthill RJ, Warneke JA, Vetto JT, Redman BG, et al. A phase 2 trial of complete resection for stage IV melanoma: results of Southwest Oncology Group Clinical Trial S9430. Cancer 2011;117: 4740-06.
19. Wasif N, Bagaria SP, Ray P, Morton DL. Does metastasectomy improve survival in patients with Stage IV melanoma? A cancer registry analysis of outcomes. J Surg Oncol 2011;104:111-5.
20. Lawson DH, Lee SJ, Tarhini AA, Margolin KA, Ernstoff MS, Kirkwood JM. E4697: 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:abstr8504.
21. 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.
22. Eggermont AM, Suciu S, SantinamiM, Testori A, Kruit WH, Marsden J, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: fi nal results of EORTC 18991, a randomised phase III trial. Lancet 2008;372:117-26.
23. Kirkwood JM, Ibrahim JG, Sosman JA, Sondak VK, Agarwala SS, Ernstoff MS, et al. High-dose interferon alfa-2b signifi cantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol 2001;19: 2370-80.
24. 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.
25. Mocellin S, Pasquali S, Rossi CR, Nitti D. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and metaanalysis. J Natl Cancer Inst 2010;102:493-501.
26. Sarnaik AA, Yu B, Yu D, Morelli D, Hall M, Bogle D, et al. Extended dose ipilimumab with a peptide vaccine: immune correlates associated with clinical benefit in patients with resected high-risk stage IIIc/IV melanoma. Clin Cancer Res 2011;17:896-906.
27. 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.
28. Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchock JD, Schmidt H, et al. Ipilimumab versus placebo after complete resection of stage III melanoma: Initial effi cacy and safety results from the EORTC 18071 phase III trial. J Clin Oncol 2014;32:5s: abstrLBA9008.
29. Eggermont AM, Suciu S, Testori A, SantinamiM, 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.
30. Mocellin S, Lens MB, Pasquali S, Pilati P, Chiarion Sileni V. Interferon alpha for the adjuvant treatment of cutaneous melanoma. Cochrane Database Syst Rev 2013;6:CD008955.
31. Verma S, Quirt I, McCready D, Bak K, Charette M, Iscoe N. Systemic review of systemic adjuvant therapy for patients at high risk for recurrent melanoma. Cancer 2006;106:1431-42.
32. Corrie PG,Marshall A, Dunn JA,Middleton MR, Nathan PD, Gore M, et al. Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, openlabel, randomised controlled phase 3 study. The Lancet Oncology 2014; 15:620-30.
33. 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.
34. Karyampudi L, Lamichhane P, Scheid AD, Kalli KR, Shreeder B, Krempski JW, et al. Accumulation of memory precursor CD8 T cells in regressing tumors following combination therapy with vaccine and anti-PD-1 antibody. Cancer Res 2014;74:2974-85.
35. Tarhini AA, Butterfield LH, Shuai Y, Gooding WE, Kalinski P, Kirkwood JM. Differing patterns of circulating regulatory T cells and myeloid-derived suppressor cells in metastatic melanoma patients receiving anti-CTLA4 antibody and interferon-alpha or TLR-9 agonist and GM-CSF with peptide vaccination. J Immunother 2012;35:702-10.
36. Tarhini AA, Edington H, Butterfi eld LH, Lin Y, Shuai Y, Tawbi H, et al. Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab. PLoS ONE 2014;9:e87705.
37. Duraiswamy J, Kaluza KM, Freeman GJ, Coukos G. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res 2013;73:3591-603.
38. 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.
39. 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:abstrLBA9003.
40. Gabrilovich DI,Nagaraj S.Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009;9:162-74.
41. Kirkwood JM, Tarhini AA, Panelli MC, Moschos SJ, Zarour HM, Butterfield LH, et al. Next generation of immunotherapy for melanoma. J Clin Oncol 2008;26:3445-55.
42. Ku GY, Yuan J, Page DB, Schroeder SE, Panageas KS, Carvajal RD, et al. Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival. Cancer 2010;116:1767-75.
43. Messina JL, Fenstermacher DA, Eschrich S, Qu X, Berglund AE, Lloyd MC, et al. 12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy? Sci Rep 2012;2:765.