Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions
Tóm tắt
Từ khóa
Tài liệu tham khảo
Hodi, 2010, Improved survival with ipilimumab in patients with metastatic melanoma, N Engl J Med, 363, 711, 10.1056/NEJMoa1003466
Robert, 2011, Ipilimumab plus dacarbazine for previously untreated metastatic melanoma, N Engl J Med, 364, 2517, 10.1056/NEJMoa1104621
Weber, 2015, 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, 375, 10.1016/S1470-2045(15)70076-8
Robert, 2015, Nivolumab in previously untreated melanoma without BRAF mutation, N Engl J Med, 372, 320, 10.1056/NEJMoa1412082
Robert, 2014, 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, 1109, 10.1016/S0140-6736(14)60958-2
Brahmer, 2015, Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer, N Engl J Med, 373, 123, 10.1056/NEJMoa1504627
Borghaei, 2015, Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer, N Engl J Med, 373, 1627, 10.1056/NEJMoa1507643
Herbst, 2016, Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial, Lancet, 387, 1540, 10.1016/S0140-6736(15)01281-7
Motzer, 2015, Nivolumab versus everolimus in advanced renal-cell carcinoma, N Engl J Med, 373, 1803, 10.1056/NEJMoa1510665
Chow, 2016, 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, 3838, 10.1200/JCO.2016.68.1478
Ferris, 2016, Nivolumab for recurrent squamous-cell carcinoma of the head and neck, N Engl J Med, 375, 1856, 10.1056/NEJMoa1602252
Ansell, 2015, PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma, N Engl J Med, 372, 311, 10.1056/NEJMoa1411087
Rosenberg, 2016, 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, 1909, 10.1016/S0140-6736(16)00561-4
Fehrenbacher, 2016, 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, 1837, 10.1016/S0140-6736(16)00587-0
Postow, 2015, Nivolumab and ipilimumab versus ipilimumab in untreated melanoma, N Engl J Med, 372, 2006, 10.1056/NEJMoa1414428
Larkin, 2015, Combined nivolumab and ipilimumab or monotherapy in untreated melanoma, N Engl J Med, 373, 23, 10.1056/NEJMoa1504030
Das, 2015, Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo, J Immunol, 194, 950, 10.4049/jimmunol.1401686
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.
Weber, 2015, Toxicities of immunotherapy for the practitioner, J Clin Oncol, 33, 2092, 10.1200/JCO.2014.60.0379
Spain, 2016, Combination immune checkpoint blockade with ipilimumab and nivolumab in the management of advanced melanoma, Expert Opin Biol Ther, 16, 389, 10.1517/14712598.2016.1141195
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).
EMA. European public assessment report Opdivo (EMA/CHMP/76688/2015).
EMA. European public assessment report Yervoy. (EMA/CHMP/557664/2011).
Eigentler, 2016, Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy, Cancer Treat Rev, 45, 7, 10.1016/j.ctrv.2016.02.003
Guyatt, 2008, GRADE: an emerging consensus on rating quality of evidence and strength of recommendations, BMJ, 336, 924, 10.1136/bmj.39489.470347.AD
ICH. Introductory guide MedDRA version 17.1. (MSSO-DI-6003-17.1.0, September 2014).
Weber, 2012, Management of immune-related adverse events and kinetics of response with ipilimumab, J Clin Oncol, 30, 2691, 10.1200/JCO.2012.41.6750
Weber, 2013, 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, 1675, 10.1002/cncr.27969
FDA. Medical review BLA 125377Orig1s000 (Yervoy); 2011 (accessed 17 Feb 2017).
Belum, 2016, Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor, Eur J Cancer, 60, 12, 10.1016/j.ejca.2016.02.010
Sibaud, 2016, Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies, Curr Opin Oncol, 28, 254, 10.1097/CCO.0000000000000290
Hofmann, 2016, Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy, Eur J Cancer, 60, 190, 10.1016/j.ejca.2016.02.025
Nayar, 2016, Toxic epidermal necrolysis-like reaction with severe satellite cell necrosis associated with nivolumab in a patient with ipilimumab refractory metastatic melanoma, J Immunother, 39, 149, 10.1097/CJI.0000000000000112
Shi, 2016, 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, 1128, 10.1001/jamadermatol.2016.2226
Naidoo, 2016, Autoimmune bullous skin disorders with immune checkpoint inhibitors targeting PD-1 and PD-L1, Cancer Immunol Res, 4, 383, 10.1158/2326-6066.CIR-15-0123
Shenoy, 2016, Pembrolizumab induced severe sclerodermoid reaction, Ann Oncol, 28, 432, 10.1093/annonc/mdw543
Beck, 2006, Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4, J Clin Oncol, 24, 2283, 10.1200/JCO.2005.04.5716
Weber, 2009, 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, 5591, 10.1158/1078-0432.CCR-09-1024
Uslu, 2015, Autoimmune colitis and subsequent CMV-induced hepatitis after treatment with ipilimumab, J Immunother, 38, 212, 10.1097/CJI.0000000000000081
Lankes, 2016, Anti-TNF-refractory colitis after checkpoint inhibitor therapy: possible role of CMV-mediated immunopathogenesis, Oncoimmunology, 5, e1128611, 10.1080/2162402X.2015.1128611
Voskens, 2013, 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, e53745, 10.1371/journal.pone.0053745
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.
Okano, 2016, Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma, Endocr J, 63, 905, 10.1507/endocrj.EJ16-0161
Mahzari, 2015, Immune checkpoint inhibitor therapy associated hypophysitis, Clin Med Insights: Endocrinol Diabetes, 8, 21
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.
Chae, 2017, A case of pembrolizumab-induced type-1 diabetes mellitus and discussion of immune checkpoint inhibitor-induced type 1 diabetes, Cancer Immunol Immunother, 66, 25, 10.1007/s00262-016-1913-7
Munakata, 2017, Fulminant type I diabetes mellitus associated with nivolumab in a patient with relapsed classical Hodgkin lymphoma, Int J Hematol, 105, 383, 10.1007/s12185-016-2101-4
Naidoo, 2015, Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies, Ann Oncol, 26, 2375, 10.1093/annonc/mdv383
Naidoo, 2017, Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy, J Clin Oncol, 35, 709, 10.1200/JCO.2016.68.2005
Nishino, 2015, Anti-PD-1-related pneumonitis during cancer immunotherapy, N Engl J Med, 373, 288, 10.1056/NEJMc1505197
EMA. Summary of product characteristics Opdivo™, version 11 Aug 2016. [accessed December 15, 2016].
Murakami, 2016, Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma, Clin Kidney J, 9, 411, 10.1093/ckj/sfw024
Jung, 2016, Nivolumab-associated acute glomerulonephritis: a case report and literature review, BMC Nephrol, 17, 188, 10.1186/s12882-016-0408-2
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.
Bronstein, 2011, Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy, AJR Am J Roentgenol, 197, W992, 10.2214/AJR.10.6198
Cappelli, 2017, Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab, Ann Rheum Dis, 76, 43, 10.1136/annrheumdis-2016-209595
Cappelli, 2017, Immune-related adverse effects of cancer immunotherapy-implications for rheumatology, Rheum Dis Clin North Am, 43, 65, 10.1016/j.rdc.2016.09.007
Sheik Ali, 2015, Drug-associated dermatomyositis following ipilimumab therapy: a novel immune-mediated adverse event associated with cytotoxic T-lymphocyte antigen 4 blockade, JAMA Dermatol, 151, 195, 10.1001/jamadermatol.2014.2233
Simeone, 2014, 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, P235, 10.1186/2051-1426-2-S3-P235
Schwab, 2016, Development of hemolytic anemia in a nivolumab-treated patient with refractory metastatic squamous cell skin cancer and chronic lymphatic leukemia, Case Rep Oncol, 9, 373, 10.1159/000447508
Kong, 2016, Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma, Melanoma Res, 26, 202, 10.1097/CMR.0000000000000232
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.
Nair, 2016, Immunotherapy-associated hemolytic anemia with pure red-cell aplasia, N Engl J Med, 374, 1096, 10.1056/NEJMc1509362
Zimmer, 2016, Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy, Eur J Cancer, 60, 210, 10.1016/j.ejca.2016.02.024
Weber, 2016, 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, 943, 10.1016/S1470-2045(16)30126-7
Hodi, 2016, 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, 1558, 10.1016/S1470-2045(16)30366-7
Tabchi, 2016, Severe agranulocytosis in a patient with metastatic non-small-cell lung cancer treated with nivolumab, Lung Cancer, 99, 123, 10.1016/j.lungcan.2016.06.026
Kopecký, 2015, Treatment possibilities of ipilimumab-induced thrombocytopenia–case study and literature review, Jpn J Clin Oncol, 45, 381, 10.1093/jjco/hyu222
Le Roy, 2016, Two cases of immune thrombocytopenia associated with pembrolizumab, Eur J Cancer, 54, 172, 10.1016/j.ejca.2015.10.073
Nguyen, 2016, Cyclosporine for dry eye associated with nivolumab: a case progressing to corneal perforation, Cornea, 35, 399, 10.1097/ICO.0000000000000724
Crews, 2015, Ipilimumab-associated retinopathy, Ophthal Surg Lasers Imag Retin, 46, 658, 10.3928/23258160-20150610-10
Hahn, 2016, Bilateral neuroretinitis and anterior uveitis following ipilimumab treatment for metastatic melanoma, J Ophthalmic Inflammat Infect, 6, 14, 10.1186/s12348-016-0082-3
Papavasileiou, 2016, Ipilimumab-induced ocular and orbital inflammation – a case series and review of the literature, Ocul Immunol Inflammat, 24, 140
McElnea, 2014, Thyroid-like ophthalmopathy in a euthyroid patient receiving Ipilimumab, Orbit, 33, 424, 10.3109/01676830.2014.949792
Modjtahedi, 2013, Multifocal bilateral choroidal neovascularization in a patient on ipilimumab for metastatic melanoma, Cutan Ocul Toxicol, 32, 341, 10.3109/15569527.2013.781618
Johnson, 2016, Fulminant myocarditis with combination immune checkpoint blockade, N Engl J Med, 375, 1749, 10.1056/NEJMoa1609214
Heinzerling, 2016, Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy, J Immunother Cancer, 4, 50, 10.1186/s40425-016-0152-y
Mehta, 2016, Myocarditis as an immune-related adverse event with ipilimumab/nivolumab combination therapy for metastatic melanoma, Melanoma Res, 26, 319, 10.1097/CMR.0000000000000251
Kushnir, 2016, Nivolumab-induced pericardial tamponade: a case report and discussion, Cardiology, 136, 49, 10.1159/000447053
Geisler, 2015, Apical ballooning and cardiomyopathy in a melanoma patient treated with ipilimumab: a case of takotsubo-like syndrome, J Immunother Cancer, 3, 4, 10.1186/s40425-015-0048-2
Yun, 2015, Late onset ipilimumab-induced pericarditis and pericardial effusion: a rare but life threatening complication, Case Rep Oncol Med, 2015, 794842
Antonia, 2016, 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, 883, 10.1016/S1470-2045(16)30098-5
Alabed, 2015, Pancreatitis secondary to anti-programmed death receptor 1 immunotherapy diagnosed by FDG PET/CT, Clin Nucl Med, 40, e528, 10.1097/RLU.0000000000000940
Schneiderbauer, 2017, PD-1 antibody-induced Guillain-Barré syndrome in a patient with metastatic melanoma, Acta Derm Venereol, 97, 395, 10.2340/00015555-2548
Wilgenhof, 2011, Anti-CTLA-4 antibody-induced Guillain-Barré syndrome in a melanoma patient, Ann Oncol, 22, 991, 10.1093/annonc/mdr028
Gaudy-Marqueste, 2013, 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, 77, 10.1097/CJI.0b013e31827807dd
Kazandjian, 2016, FDA approval summary: nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy, Oncologist, 21, 634, 10.1634/theoncologist.2015-0507
Williams, 2016, Association of autoimmune encephalitis with combined immune checkpoint inhibitor treatment for metastatic cancer, JAMA Neurol, 73, 928, 10.1001/jamaneurol.2016.1399
Maurice, 2015, Subacute CNS demyelination after treatment with nivolumab for melanoma, Cancer Immunol Res, 3, 1299, 10.1158/2326-6066.CIR-15-0141
Liao, 2014, Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma, Neuro Oncol, 16, 589, 10.1093/neuonc/nou001
Loochtan, 2015, Myasthenia gravis associated with ipilimumab and nivolumab in the treatment of small cell lung cancer, Muscle Nerve, 52, 307, 10.1002/mus.24648
Johnson, 2015, Myasthenia gravis induced by ipilimumab in patients with metastatic melanoma, J Clin Oncol, 33, e122, 10.1200/JCO.2013.51.1683
Hottinger, 2016, Neurologic complications of immune checkpoint inhibitors, Curr Opin Neurol, 29, 806, 10.1097/WCO.0000000000000391
Weber, 2013, Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma, J Clin Oncol, 31, 4311, 10.1200/JCO.2013.51.4802
Manousakis, 2013, Multifocal radiculoneuropathy during ipilimumab treatment of melanoma, Muscle Nerve, 48, 440, 10.1002/mus.23830
Abdel-Wahab, 2016, Adverse events associated with immune checkpoint blockade in patients with cancer: a systematic review of case reports, PLoS ONE, 11, e0160221, 10.1371/journal.pone.0160221
Vogel, 2012, Ipilimumab-induced sarcoidosis in a patient with metastatic melanoma undergoing complete remission, J Clin Oncol, 30, e7, 10.1200/JCO.2011.37.9693
Cotliar, 2016, Pembrolizumab-associated sarcoidosis, JAAD Case Rep, 2, 290, 10.1016/j.jdcr.2016.06.004
Cousin, 2016, Pulmonary sarcoidosis induced by the anti-PD1 monoclonal antibody pembrolizumab, Ann Oncol, 27, 1178, 10.1093/annonc/mdw125
Suozzi, 2016, Immune-related sarcoidosis observed in combination ipilimumab and nivolumab therapy, JAAD Case Rep, 2, 264, 10.1016/j.jdcr.2016.05.002
Montaudié, 2017, Pulmonary sarcoid-like granulomatosis induced by nivolumab, Br J Dermatol, 176, 1060, 10.1111/bjd.14808
Danlos, 2016, Nivolumab-induced sarcoid-like granulomatous reaction in a patient with advanced melanoma, Chest, 149, e133-6, 10.1016/j.chest.2015.10.082
Manusow, 2014, Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma, J Immunother Cancer, 2, 41, 10.1186/s40425-014-0041-1
Minor, 2013, Lymphocytic vasculitis of the uterus in a patient with melanoma receiving ipilimumab, J Clin Oncol, 31, e356, 10.1200/JCO.2012.47.5095
Goldstein, 2014, Drug-associated polymyalgia rheumatica/giant cell arteritis occurring in two patients after treatment with ipilimumab, an antagonist of ctla-4, Arthritis Rheumatol, 66, 768, 10.1002/art.38282
Aya, 2017, Vasculitic neuropathy induced by pembrolizumab, Ann Oncol, 28, 433, 10.1093/annonc/mdw613
Khoja, 2016, Eosinophilic fasciitis and acute encephalopathy toxicity from pembrolizumab treatment of a patient with metastatic melanoma, Cancer Immunol Res, 4, 175, 10.1158/2326-6066.CIR-15-0186
Maul, 2016, Successful anti-PD-1 antibody treatment in a metastatic melanoma patient with known severe autoimmune disease, J Immunother, 39, 188, 10.1097/CJI.0000000000000118
Menzies, 2017, Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab, Ann Oncol, 28, 368, 10.1093/annonc/mdw443
Johnson, 2016, Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders, JAMA Oncol, 2, 234, 10.1001/jamaoncol.2015.4368
Boutros, 2016, Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination, Nat Rev Clin Oncol, 13, 473, 10.1038/nrclinonc.2016.58
Weber, 2017, Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma, J Clin Oncol, 35, 785, 10.1200/JCO.2015.66.1389
Champiat, 2016, Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper, Ann Oncol, 27, 559, 10.1093/annonc/mdv623
Friedman, 2016, Treatment of the immune-related adverse effects of immune checkpoint inhibitors: a review, JAMA Oncol, 2, 1346, 10.1001/jamaoncol.2016.1051
Michot, 2016, Immune-related adverse events with immune checkpoint blockade: a comprehensive review, Eur J Cancer, 54, 139, 10.1016/j.ejca.2015.11.016
Ciccarese, 2016, New toxicity profile for novel immunotherapy agents: focus on immune-checkpoint inhibitors, Expert Opin Drug Metab Toxicol, 12, 57, 10.1517/17425255.2016.1120287
Dadu, 2016, Managing adverse events with immune checkpoint agents, Cancer J, 22, 121, 10.1097/PPO.0000000000000186
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.
Sharma, 2016, 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, 225
Nishino, 2016, Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis, JAMA Oncol, 2, 1607, 10.1001/jamaoncol.2016.2453
Sivendran, 2014, Adverse event reporting in cancer clinical trial publications, J Clin Oncol, 32, 83, 10.1200/JCO.2013.52.2219
Sivendran, 2016, Adverse event reporting in oncology clinical trials - lost in translation?, Expert Opin Drug Saf, 15, 893, 10.1080/14740338.2016.1175429
Chen, 2015, A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors, Ann Oncol, 26, 1824, 10.1093/annonc/mdv182
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.
FDA. FDA Approved Patient Information Yervoy (ipilimumab), March 2011.