Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions

Cancer Treatment Reviews

Volumn 57, Issue , 2017, Pages 36-49

  Hassel, Jessica C ^a   Heinzerling, Lucie ^b   Aberle, Jens ^c   Bähr, Oliver ^d   Eigentler, Thomas K ^e   Grimm, Marc Oliver ^f   Grünwald, Victor ^g   Leipe, Jan ^h   Reinmuth, Niels ⁱ   Tietze, Julia K ^j   Trojan, Jörg ^d   Zimmer, Lisa ^k   Gutzmer, Ralf ^g  

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^b UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^c UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^d UNIVERSITY HOSPITAL FRANKFURT   (Germany)

^e UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^f JENA UNIVERSITY HOSPITAL   (Germany)

^g HANNOVER MEDICAL SCHOOL   (Germany)

^h UNIVERSITY OF MUNICH   (Germany)

ⁱ ASKLEPIOS FACHKLINIKEN MÜNCHEN GAUTING   (Germany)

^j LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^k UNIVERSITY HOSPITAL ESSEN   (Germany)

more..

Author keywords

Adverse drug reaction; Immunotherapy; Ipilimumab; Nivolumab; PD 1, CTLA 4

Indexed keywords

AMYLASE; ANTIHISTAMINIC AGENT; CORTICOSTEROID; GLUCOCORTICOID; IMMUNOGLOBULIN; INFLIXIMAB; IPILIMUMAB; METHYLPREDNISOLONE; MYCOPHENOLATE MOFETIL; NIVOLUMAB; TRIACYLGLYCEROL LIPASE; ANTINEOPLASTIC AGENT; CTLA4 PROTEIN, HUMAN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; MONOCLONAL ANTIBODY; PDCD1 PROTEIN, HUMAN; PROGRAMMED DEATH 1 RECEPTOR;

ACUTE HEPATITIS; ACUTE KIDNEY FAILURE; ADRENAL DISEASE; ADVERSE DRUG REACTION; AGRANULOCYTOSIS; ALLERGIC REACTION; ARTHRALGIA; ARTHRITIS; AUTOIMMUNE HEPATITIS; BULLOUS PEMPHIGOID; COLITIS; DEMYELINATION; DERMATITIS; DIABETES MELLITUS; DIARRHEA; DRUG HYPERSENSITIVITY; DRUG SAFETY; ENTEROCOLITIS; ERYTHEMA; GUILLAIN BARRE SYNDROME; HAND FOOT SYNDROME; HEPATITIS; HUMAN; HYPERSENSITIVITY; HYPERTHYROIDISM; HYPOPHYSITIS; HYPOPIGMENTATION; HYPOTHYROIDISM; IDIOPATHIC THROMBOCYTOPENIC PURPURA; INCIDENCE; INFUSION RELATED REACTION; INTERSTITIAL LUNG DISEASE; INTERSTITIAL NEPHRITIS; KIDNEY FAILURE; LICHENOID ERUPTION; LIVER DISEASE; LIVER TOXICITY; MEDICAL ASSESSMENT; MELANOMA; MONOTHERAPY; MORBIDITY; MYALGIA; MYOCARDITIS; NEPHRITIS; PANCREATITIS; PHOTOSENSITIVITY; PNEUMONIA; PRURITUS; RASH; REVIEW; URTICARIA; UVEITIS; VITILIGO; ANTAGONISTS AND INHIBITORS;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CTLA-4 ANTIGEN; HUMANS; MELANOMA; PROGRAMMED CELL DEATH 1 RECEPTOR;

EID: 85019634658     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2017.05.003     Document Type: Review

References (127)

1. Hodi, F.S., O'Day, S.J., McDermott, D.F., Weber, R.W., Sosman, J.A., Haanen, J.B., et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363 (2010), 711–723.
2. Robert, C., Thomas, L., Bondarenko, I., O'Day, S., M, D.J., Garbe, C., et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364 (2011), 2517–2526.
3. Weber, J.S., D'Angelo, S.P., Minor, D., Hodi, F.S., 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 16 (2015), 375–384.
4. Robert, C., Long, G.V., Brady, B., Dutriaux, C., Maio, M., Mortier, L., et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372 (2015), 320–330.
5. Robert, C., Ribas, A., Wolchok, J.D., Hodi, F.S., 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. The Lancet 384 (2014), 1109–1117.
6. Brahmer, J., Reckamp, K.L., Baas, P., Crinò, L., Eberhardt, W.E., Poddubskaya, E., et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373 (2015), 123–135.
7. Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D.R., Steins, M., Ready, N.E., et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373 (2015), 1627–1639.
8. Herbst, R.S., Baas, P., Kim, D.-W., Felip, E., Pérez-Gracia, J.L., Han, J.Y., et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387 (2016), 1540–1550.
9. Motzer, R.J., Escudier, B., McDermott, D.F., George, S., Hammers, H.J., Srinivas, S., et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373 (2015), 1803–1813.
10. Chow, L.Q., Haddad, R., Gupta, S., Mahipal, A., Mehra, R., Tahara, M., et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the phase Ib KEYNOTE-012 expansion cohort. J Clin Oncol 34 (2016), 3838–3845.
11. Ferris, R.L., Blumenschein, G. Jr, Fayette, J., Guigay, J., Colevas, A.D., Licitra, L., et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375 (2016), 1856–1867.
12. Ansell, S.M., Lesokhin, A.M., Borrello, I., Halwani, A., Scott, E.C., Gutierrez, M., et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 372 (2015), 311–319.
13. Rosenberg, J.E., Hoffman-Censits, J., Powles, T., van der Heijden, M.S., Balar, A.V., Necchi, A., et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387 (2016), 1909–1920.
14. Fehrenbacher, L., Spira, A., Ballinger, M., Kowanetz, M., Vansteenkiste, J., Mazieres, J., et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 387 (2016), 1837–1846.
15. Postow, M.A., Chesney, J., Pavlick, A.C., Robert, C., Grossmann, K., McDermott, D., et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 372 (2015), 2006–2017.
16. Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J.J., Cowey, C.L., Lao, C.D., et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373 (2015), 23–34.
17. Mellman, I., Coukos, G., Dranoff, G., Cancer immunotherapy comes of age. Nature 480 (2011), 480–489.
18. Das, R., Verma, R., Sznol, M., Boddupalli, C.S., Gettinger, S.N., Kluger, H., et al. Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J Immunol 194 (2015), 950–959.
19. Larkin J, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Cowey CL, Lao CD, et al. Overall survival (OS) results from a phase III trial of nivolumab (NIVO) combined with ipilimumab (IPI) in treatment-naïve patients with advanced melanoma (CheckMate 067). In: Proceedings of the 107th annual meeting of the american association for cancer research; 2017 Apr 1–5; Washington, DC. Philadelphia (PA): AACR; 2017. Abstract CT075.
20. Weber, J.S., Yang, J.C., Atkins, M.B., Disis, M.L., Toxicities of immunotherapy for the practitioner. J Clin Oncol 33 (2015), 2092–2099.
21. Spain, L., Larkin, J., Combination immune checkpoint blockade with ipilimumab and nivolumab in the management of advanced melanoma. Expert Opin Biol Ther 16 (2016), 389–396.
22. EMA. European public assessment report Opdivo. [Type-II variation (line extension) for use of nivolumab in combination with ipilimumab in adv. melanoma.] (EMA/CHMP/215704/2016).
23. EMA. European public assessment report Opdivo (EMA/CHMP/76688/2015).
24. EMA. European public assessment report Yervoy. (EMA/CHMP/557664/2011).
25. Eigentler, T.K., Hassel, J.C., Berking, C., Aberle, J., Bachmann, O., Grünwald, V., et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev 45 (2016), 7–18.
26. Guyatt, G.H., Oxman, A.D., Vist, G.E., Kunz, R., Falck-Ytter, Y., Alonso-Coello, P., et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336 (2008), 924–926.
27. ICH. Introductory guide MedDRA version 17.1. (MSSO-DI-6003-17.1.0, September 2014).
28. Weber, J.S., Kähler, K.C., Hauschild, A., Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 30 (2012), 2691–2697.
29. Weber, J.S., Dummer, R., de Pril, V., Lebbé, C., Hodi, F.S., MDX010-20 Investigators. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer 119 (2013), 1675–1682.
30. FDA. Medical review BLA 125377Orig1s000 (Yervoy); 2011 (accessed 17 Feb 2017).
31. Belum, V.R., Benhuri, B., Postow, M.A., Hellmann, M.D., Lesokhin, A.M., Segal, N.H., et al. Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor. Eur J Cancer 60 (2016), 12–25.
32. Sibaud, V., Meyer, N., Lamant, L., Vigarios, E., Mazieres, J., Delord, J.P., Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies. Curr Opin Oncol 28 (2016), 254–263.
33. Hofmann, L., Forschner, A., Loquai, C., Goldinger, S.M., Zimmer, L., Ugurel, S., et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer 60 (2016), 190–209.
34. Nayar, N., Briscoe, K., Fernandez, Penas P., Toxic epidermal necrolysis-like reaction with severe satellite cell necrosis associated with nivolumab in a patient with ipilimumab refractory metastatic melanoma. J Immunother 39 (2016), 149–152.
35. Shi, V.J., Rodic, N., Gettinger, S., Leventhal, J.S., Neckman, J.P., Girardi, M., et al. Clinical and histologic features of lichenoid mucocutaneous eruptions due to anti-programmed cell death 1 and anti-programmed cell death ligand 1 immunotherapy. JAMA Dermatol 152 (2016), 1128–1136.
36. Naidoo, J., Schindler, K., Querfeld, C., Busam, K., Cunningham, J., Page, D.B., et al. Autoimmune bullous skin disorders with immune checkpoint inhibitors targeting PD-1 and PD-L1. Cancer Immunol Res 4 (2016), 383–389.
37. Shenoy, N., Esplin, B., Barbosa, N., Wieland, C., Thanarajasingam, U., Markovic, S., Pembrolizumab induced severe sclerodermoid reaction. Ann Oncol 28 (2016), 432–433.
38. Beck, K.E., Blansfield, J.A., Tran, K.Q., Feldman, A.L., Hughes, M.S., Royal, R.E., et al. Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J Clin Oncol 24 (2006), 2283–2289.
39. Weber, J., Thompson, J.A., Hamid, O., Minor, D., Amin, A., Ron, I., et al. A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin Cancer Res 15 (2009), 5591–5598.
40. Uslu, U., Agaimy, A., Hundorfean, G., Harrer, T., Schuler, G., Heinzerling, L., et al. Autoimmune colitis and subsequent CMV-induced hepatitis after treatment with ipilimumab. J Immunother 38 (2015), 212–215.
41. Lankes, K., Hundorfean, G., Harrer, T., Pommer, A.J., Agaimy, A., Angelovska, I., et al. Anti-TNF-refractory colitis after checkpoint inhibitor therapy: possible role of CMV-mediated immunopathogenesis. Oncoimmunology, 5, 2016, e1128611.
42. Voskens, C.J., Goldinger, S.M., Loquai, C., Robert, C., Kaehler, K.C., Berking, C., et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. PLoS ONE, 8, 2013, e53745.
43. Verma I, Modi A, Tripathi H, Agrawal A. Nivolumab causing painless thyroiditis in a patient with adenocarcinoma of the lung. BMJ Case Rep; 2016; pii: bcr2015213692. doi: http://dx.doi.org/10.1136/bcr-2015-213692.
44. McMillen, B., Dhillon, M.S., Yong-Yow, S., A rare case of thyroid storm. BMJ Case Rep, 2016, 10.1136/bcr-2016-214603.
45. Okano, Y., Satoh, T., Horiguchi, K., Toyoda, M., Osaki, A., Matsumoto, S., et al. Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma. Endocr J 63 (2016), 905–912.
46. Mahzari, M., Liu, D., Arnaout, A., Lochnan, H., Immune checkpoint inhibitor therapy associated hypophysitis. Clin Med Insights: Endocrinol Diabetes 8 (2015), 21–28.
47. Trainer H, Hulse P, Higham CE, Trainer P, Lorigan P. Hyponatraemia secondary to nivolumab-induced primary adrenal failure. Endocrinol Diabetes Metab Case Rep 2016; 2016 [Epub ahead of print] pii: 16-0108.
48. Chae, Y.K., Chiec, L., Mohindra, N., Gentzler, R., Patel, J., Giles, F., A case of pembrolizumab-induced type-1 diabetes mellitus and discussion of immune checkpoint inhibitor-induced type 1 diabetes. Cancer Immunol Immunother 66 (2017), 25–32.
49. Munakata, W., Ohashi, K., Yamauchi, N., Tobinai, K., Fulminant type I diabetes mellitus associated with nivolumab in a patient with relapsed classical Hodgkin lymphoma. Int J Hematol 105 (2017), 383–386.
50. Naidoo, J., Page, D.B., Li, B.T., Connell, L.C., Schindler, K., Lacouture, M.E., et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol 26 (2015), 2375–2391.
51. Naidoo, J., Wang, X., Woo, K.M., Iyriboz, T., Halpenny, D., Cunningham, J., et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clin Oncol 35 (2017), 709–717.
52. Nishino, M., Sholl, L.M., Hodi, F.S., Hatabu, H., Ramaiya, N.H., Anti-PD-1-related pneumonitis during cancer immunotherapy. N Engl J Med 373 (2015), 288–290.
53. EMA. Summary of product characteristics Opdivo™, version 11 Aug 2016. [accessed December 15, 2016].
54. Murakami, N., Borges, T.J., Yamashita, M., Riella, L.V., Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma. Clin Kidney J 9 (2016), 411–417.
55. Jung, K., Zeng, X., Bilusic, M., Nivolumab-associated acute glomerulonephritis: a case report and literature review. BMC Nephrol, 17, 2016, 188.
56. Capelli LC, Gutierrez AK, Bingham CO 3rd, Shah AA. Rheumatic and musculoskeletal immune-related adverse events due to immune checkpoint inhibitors: a systematic review of the literature. Arthritis care res (Hoboken); 2016. December20 [Epub ahead of print] doi: http://dx.doi.org/10.1002/acr.23177.
57. Bronstein, Y., Ng, C.S., Hwu, P., Hwu, H.J., Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy. AJR Am J Roentgenol 197 (2011), W992–W1000.
58. Cappelli, L.C., Gutierrez, A.K., Baer, A.N., Albayda, J., Manno, R.L., Haque, U., et al. Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab. Ann Rheum Dis 76 (2017), 43–50.
59. Cappelli, L.C., Shah, A.A., Bingham, C.O. 3rd., Immune-related adverse effects of cancer immunotherapy-implications for rheumatology. Rheum Dis Clin North Am 43 (2017), 65–78.
60. Sheik Ali, S., Goddard, A.L., Luke, J.J., Donahue, H., Todd, D.J., Werchniak, A., et al. Drug-associated dermatomyositis following ipilimumab therapy: a novel immune-mediated adverse event associated with cytotoxic T-lymphocyte antigen 4 blockade. JAMA Dermatol 151 (2015), 195–199.
61. Simeone, E., Romano, M.F., Grimaldi, A.M., Esposito, A., Curvietto, M., Paone, M., et al. High expression of a spliced variant of FKBP51 in peripheral blood mononuclear cells of melanoma patients may be related to PDL-1 on tumour and predictive of response to Ipilimumab. J Immunother Cancer, 2(Suppl. 3), 2014, P235.
62. Schwab, K.S., Heine, A., Weimann, T., Kristiansen, G., Brossart, P., Development of hemolytic anemia in a nivolumab-treated patient with refractory metastatic squamous cell skin cancer and chronic lymphatic leukemia. Case Rep Oncol 9 (2016), 373–378.
63. Kong, B.Y., Micklethwaite, K.P., Swaminathan, S., Kefford, R.F., Carlino, M.S., Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma. Melanoma Res 26 (2016), 202–204.
64. Tardy MP, Gastaud L, Boscagli A, Peyrade F, Gallamini A, Thyss A. Autoimmune hemolytic anemia after nivolumab treatment in Hodgkin lymphoma responsive to immunosuppressive treatment. A case report. Hematol Oncol; 2016. August 19. [Epub ahead of print]. doi: http://dx.doi.org/10.1002/hon.2338.
65. Nair, R., Gheith, S., Nair, S.G., Immunotherapy-associated hemolytic anemia with pure red-cell aplasia. N Engl J Med 374 (2016), 1096–1097.
66. Zimmer, L., Goldinger, S.M., Hofmann, L., Loquai, C., Ugurel, S., Thomas, I., et al. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer 60 (2016), 210–225.
67. Weber, J.S., Gibney, G., Sullivan, R.J., Sosman, J.A., Slingluff, C.L. Jr, Lawrence, D.P., et al. Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomised, phase 2 trial. Lancet Oncol 17 (2016), 943–955.
68. Hodi, F.S., Chesney, J., Pavlick, A.C., Robert, C., Grossmann, K.F., McDermott, D.F., et al. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol 17 (2016), 1558–1568.
69. Tabchi, S., Weng, X., Blais, N., Severe agranulocytosis in a patient with metastatic non-small-cell lung cancer treated with nivolumab. Lung Cancer 99 (2016), 123–126.
70. Kopecký, J., Trojanová, P., Kubeček, O., Kopecký, O., Treatment possibilities of ipilimumab-induced thrombocytopenia–case study and literature review. Jpn J Clin Oncol 45 (2015), 381–384.
71. Le Roy, A., Kempf, E., Ackermann, F., Routier, E., Robert, C., Turpin, A., et al. Two cases of immune thrombocytopenia associated with pembrolizumab. Eur J Cancer 54 (2016), 172–174.
72. Nguyen, A.T., Elia, M., Materin, M.A., Sznol, M., Chow, J., Cyclosporine for dry eye associated with nivolumab: a case progressing to corneal perforation. Cornea 35 (2016), 399–401.
73. Crews, J., Agarwal, A., Jack, L., Xu, D., Do, D.V., Nguyen, Q.D., Ipilimumab-associated retinopathy. Ophthal Surg Lasers Imag Retin 46 (2015), 658–660.
74. Hahn, L., Pepple, K.L., Bilateral neuroretinitis and anterior uveitis following ipilimumab treatment for metastatic melanoma. J Ophthalmic Inflammat Infect, 6, 2016, 14.
75. Papavasileiou, E., Prasad, S., Freitag, S.K., Sobrin, L., Lobo, A.M., Ipilimumab-induced ocular and orbital inflammation – a case series and review of the literature. Ocul Immunol Inflammat 24 (2016), 140–144.
76. McElnea, E., Ní Mhéalóid, A., Moran, S., Kelly, R., Fulcher, T., Thyroid-like ophthalmopathy in a euthyroid patient receiving Ipilimumab. Orbit 33 (2014), 424–427.
77. Modjtahedi, B.S., Maibach, H., Park, S., Multifocal bilateral choroidal neovascularization in a patient on ipilimumab for metastatic melanoma. Cutan Ocul Toxicol 32 (2013), 341–343.
78. Johnson, D.B., Balko, J.M., Compton, M.L., Chalkias, S., Gorham, J., Xu, Y., et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 375 (2016), 1749–1755.
79. Heinzerling, L., Ott, P.A., Hodi, F.S., Husain, A.N., Tajmir-Riahi, A., Tawbi, H., et al. Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy. J Immunother Cancer, 4, 2016, 50.
80. Mehta, A., Gupta, A., Hannallah, F., Koshy, T., Reimold, S., Myocarditis as an immune-related adverse event with ipilimumab/nivolumab combination therapy for metastatic melanoma. Melanoma Res 26 (2016), 319–320.
81. Kushnir, I., Wolf, I., Nivolumab-induced pericardial tamponade: a case report and discussion. Cardiology 136 (2016), 49–51.
82. Geisler, J.P., Raad, R.A., Esaian, D., Sharon, E., Schwartz, D.R., Apical ballooning and cardiomyopathy in a melanoma patient treated with ipilimumab: a case of takotsubo-like syndrome. J Immunother Cancer, 3, 2015, 4.
83. Yun, S., Vincelette, N.D., Mansour, I., Motamed, S., Late onset ipilimumab-induced pericarditis and pericardial effusion: a rare but life threatening complication. Case Rep Oncol Med, 2015, 2015, 794842.
84. Antonia, S.J., López-Martin, J.A., Bendell, J., Ott, P.A., Taylor, M., Eder, J.P., et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol 17 (2016), 883–895.
85. Alabed, Y.Z., Aghayev, A., Sakellis, C., van den Abbeele, A.D., Pancreatitis secondary to anti-programmed death receptor 1 immunotherapy diagnosed by FDG PET/CT. Clin Nucl Med 40 (2015), e528–e529.
86. Schneiderbauer, R., Schneiderbauer, M., Wick, W., Enk, A.H., Haenssle, H.A., Hassel, J.C., PD-1 antibody-induced Guillain-Barré syndrome in a patient with metastatic melanoma. Acta Derm Venereol 97 (2017), 395–396.
87. Wilgenhof, S., Neyns, B., Anti-CTLA-4 antibody-induced Guillain-Barré syndrome in a melanoma patient. Ann Oncol 22 (2011), 991–993.
88. Gaudy-Marqueste, C., Monestier, S., Franques, J., Cantais, E., Richard, M.A., Grob, J.J., A severe case of ipilimumab-induced guillain-barré syndrome revealed by an occlusive enteric neuropathy: a differential diagnosis for ipilimumab-induced colitis. J Immunother 36 (2013), 77–78.
89. Kazandjian, D., Suzman, D.L., Blumenthal, G., Mushti, S., He, K., Libeg, M., et al. FDA approval summary: nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Oncologist 21 (2016), 634–642.
90. Williams, T.J., Benavides, D.R., Patrice, K.A., Dalmau, J.O., de Ávila, A.L., Le, D.T., et al. Association of autoimmune encephalitis with combined immune checkpoint inhibitor treatment for metastatic cancer. JAMA Neurol 73 (2016), 928–933.
91. Maurice, C., Schneider, R., Kiehl, T.R., Bavi, P., Roehrl, M.H., Mason, W.P., et al. Subacute CNS demyelination after treatment with nivolumab for melanoma. Cancer Immunol Res 3 (2015), 1299–1302.
92. Liao, B., Shroff, S., Kamiya-Matsuoka, C., Tummala, S., Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma. Neuro Oncol 16 (2014), 589–593.
93. Loochtan, A.I., Nickolich, M.S., Hobson-Webb, L.D., Myasthenia gravis associated with ipilimumab and nivolumab in the treatment of small cell lung cancer. Muscle Nerve 52 (2015), 307–308.
94. Johnson, D.B., Saranga-Perry, V., Lavin, P.J., Burnette, W.B., Clark, S.W., Uskavitch, D.R., et al. Myasthenia gravis induced by ipilimumab in patients with metastatic melanoma. J Clin Oncol 33 (2015), e122–e124.
95. Hottinger, A.F., Neurologic complications of immune checkpoint inhibitors. Curr Opin Neurol 29 (2016), 806–812.
96. Weber, J.S., Kudchadkar, R.R., Yu, B., Gallenstein, D., Horak, C.E., Inzunza, H.D., et al. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol 31 (2013), 4311–4318.
97. Manousakis, G., Koch, J., Sommerville, R.B., El-Dokla, A., Harms, M.B., Al-Lozi, M.T., et al. Multifocal radiculoneuropathy during ipilimumab treatment of melanoma. Muscle Nerve 48 (2013), 440–444.
98. Abdel-Wahab, N., Shah, M., Suarez-Almazor, M.E., Adverse events associated with immune checkpoint blockade in patients with cancer: a systematic review of case reports. PLoS ONE, 11, 2016, e0160221.
99. Vogel, W.V., Guislain, A., Kvistborg, P., Schumacher, T.N., Haanen, J.B., Blank, C.U., Ipilimumab-induced sarcoidosis in a patient with metastatic melanoma undergoing complete remission. J Clin Oncol 30 (2012), e7–e10.
100. Cotliar, J., Querfeld, C., Boswell, W.J., Raja, N., Raz, D., Chen, R., Pembrolizumab-associated sarcoidosis. JAAD Case Rep 2 (2016), 290–293.
101. Cousin, S., Toulmonde, M., Kind, M., Cazeau, A.L., Bechade, D., Coindre, J.M., et al. Pulmonary sarcoidosis induced by the anti-PD1 monoclonal antibody pembrolizumab. Ann Oncol 27 (2016), 1178–1179.
102. Suozzi, K.C., Stahl, M., Ko, C.J., Chiang, A., Gettinger, S.N., Siegel, M.D., et al. Immune-related sarcoidosis observed in combination ipilimumab and nivolumab therapy. JAAD Case Rep 2 (2016), 264–268.
103. Montaudié, H., Pradelli, J., Passeron, T., Lacour, J.P., Leroy, S., et al. Pulmonary sarcoid-like granulomatosis induced by nivolumab. Br J Dermatol 176 (2017), 1060–1063.
104. Danlos, F.X., Pagès, C., Baroudjian, B., Vercellino, L., Battistella, M., Mimoun, M., et al. Nivolumab-induced sarcoid-like granulomatous reaction in a patient with advanced melanoma. Chest, 149, 2016, e133-6.
105. Manusow, J.S., Khoja, L., Pesin, N., Joshua, A.M., Mandelcorn, E.D., Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma. J Immunother Cancer, 2, 2014, 41.
106. Minor, D.R., Bunker, S.R., Doyle, J., Lymphocytic vasculitis of the uterus in a patient with melanoma receiving ipilimumab. J Clin Oncol, 31, 2013, e356.
107. Goldstein, B.L., Gedmintas, L., Todd, D.J., Drug-associated polymyalgia rheumatica/giant cell arteritis occurring in two patients after treatment with ipilimumab, an antagonist of ctla-4. Arthritis Rheumatol 66 (2014), 768–769.
108. Aya, F., Ruiz-Esquide, V., Viladot, M., Font, C., Prieto-González, S., Prat, A., et al. Vasculitic neuropathy induced by pembrolizumab. Ann Oncol 28 (2017), 433–434.
109. Khoja, L., Maurice, C., Chappell, M., MacMillan, L., Al-Habeeb, A.S., Al-Faraidy, N., et al. Eosinophilic fasciitis and acute encephalopathy toxicity from pembrolizumab treatment of a patient with metastatic melanoma. Cancer Immunol Res 4 (2016), 175–178.
110. Maul, L.V., Weichenthal, M., Kähler, K.C., Hauschild, A., et al. Successful anti-PD-1 antibody treatment in a metastatic melanoma patient with known severe autoimmune disease. J Immunother 39 (2016), 188–190.
111. Menzies, A.M., Johnson, D.B., Ramanujam, S., Atkinson, V.G., Wong, A.N., Park, J.J., et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol 28 (2017), 368–376.
112. Johnson, D.B., Sullivan, R.J., Ott, P.A., Carlino, M.S., Khushalani, N.I., Ye, F., et al. Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncol 2 (2016), 234–240.
113. Boutros, C., Tarhini, A., Routier, E., Lambotte, O., Ladurie, F.L., Carbonnel, F., et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol 13 (2016), 473–486.
114. Weber, J.S., Hodi, F.S., Wolchok, J.D., Topalian, S.L., Schadendorf, D., Larkin, J., et al. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J Clin Oncol 35 (2017), 785–792.
115. Champiat, S., Lambotte, O., Barreau, E., Belkhir, R., Berdelou, A., Carbonnel, F., et al. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol 27 (2016), 559–574.
116. Friedman, C.F., Proverbs-Singh, T.A., Postow, M.A., Treatment of the immune-related adverse effects of immune checkpoint inhibitors: a review. JAMA Oncol 2 (2016), 1346–1353.
117. Michot, J.M., Bigenwald, C., Champiat, S., Collins, M., Carbonnel, F., Postel-Vinay, S., et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 54 (2016), 139–148.
118. Ciccarese, C., Alfieri, S., Santoni, M., Santini, D., Brunelli, M., Bergamini, C., et al. New toxicity profile for novel immunotherapy agents: focus on immune-checkpoint inhibitors. Expert Opin Drug Metab Toxicol 12 (2016), 57–75.
119. Dadu, R., Zobniw, C., Diab, A., Managing adverse events with immune checkpoint agents. Cancer J 22 (2016), 121–129.
120. Hammers HJ, Plimack ER, Infante JR, Rini BI, McDermott DM, Ernstoff M, et al. Expanded cohort results from CheckMate 016: a phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC). J Clin Oncol 2015;33(suppl):abstr 4516.
121. Sharma, P., Callahan, M.K., Calvo, E., Kin, J.W., de Braud, F., Ott, P.A., et al. Efficacy and safety of nivolumab plus ipilimumab in metastatic urothelial carcinoma: first results from the phase I/II CheckMate 032 study. J Immunther Cancer, 4(Suppl 2), 2016, 225.
122. Nishino, M., Giobbie-Hurder, A., Hatabu, H., Ramaiya, N.H., Hodi, F.S., Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis. JAMA Oncol 2 (2016), 1607–1616.
123. Sivendran, S., Latif, A., McBride, R.B., Stensland, K.D., Wisnivesky, J., Haines, L., et al. Adverse event reporting in cancer clinical trial publications. J Clin Oncol 32 (2014), 83–89 Erratum in: J Clin Oncol 2014;32:866.
124. Sivendran, S., Galsky, M.D., Adverse event reporting in oncology clinical trials - lost in translation?. Expert Opin Drug Saf 15 (2016), 893–896.
125. Chen, T.W., Razak, A.R., Bedard, P.L., Siu, L.L., Hansen, A.R., A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors. Ann Oncol 26 (2015), 1824–1829.
126. Friedman CF, Clark V, Raikhel AV, Barz T, Shoushtari AN, Momtaz P et al. Thinking critically about classifying adverse events: incidence of pancreatitis in patients treated with nivolumab + ipilimumab. J Natl Cancer Inst 2016;109. April 2017 [Epub ahead of print] doi: 10.1093/jnci/djw260.
127. FDA. FDA Approved Patient Information Yervoy (ipilimumab), March 2011.