Advances on immune-related adverse events associated with immune checkpoint inhibitors
Yong Fan1, Yan Geng1, Lin Shen2, Zhuoli Zhang1()
1. Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing 100034, China 2. Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.
Melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, primary mediastinal large B cell lymphoma, urothelial carcinoma, microsatellite instability-high cancer, gastric cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma
Nivolumab
Anti-PD-1 antibody
2014
Opdivo
Bristol-Myers Squibb
Melanoma, non-small cell lung cancer, small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, colorectal cancer, hepatocellular carcinoma
Cemiplimab
Anti-PD-1 antibody
2018
Libtayo
Regeneron Pharmaceuticals
Cutaneous squamous cell carcinoma
Atezolizumab
Anti-PD-L1 antibody
2016
Tecentriq
Genentech
Urothelial carcinoma, non-small cell lung cancer, triple-negative breast cancer, small cell lung cancer,
Durvalumab
Anti-PD-L1 antibody
2017
Imfinzi
AstraZeneca
Urothelial carcinoma, non-small cell lung cancer
Avelumab
Anti-PD-L1 antibody
2017
Bavencio
EMD Serono
Merkel cell carcinoma, urothelial carcinoma
Tab.1
1
J Ferlay, I Soerjomataram, R Dikshit, S Eser, C Mathers, M Rebelo, DM Parkin, D Forman, F Bray. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136(5): E359–E386 https://doi.org/10.1002/ijc.29210
pmid: 25220842
2
W Chen, R Zheng, PD Baade, S Zhang, H Zeng, F Bray, A Jemal, XQ Yu, J He. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66(2): 115–132 https://doi.org/10.3322/caac.21338
pmid: 26808342
3
A Urruticoechea, R Alemany, J Balart, A Villanueva, F Viñals, G Capellá. Recent advances in cancer therapy: an overview. Curr Pharm Des 2010; 16(1): 3–10 https://doi.org/10.2174/138161210789941847
pmid: 20214614
J Inthagard, J Edwards, AK Roseweir. Immunotherapy: enhancing the efficacy of this promising therapeutic in multiple cancers. Clin Sci (Lond) 2019; 133(2): 181–193 https://doi.org/10.1042/CS20181003
pmid: 30659159
7
L Pai-Scherf, GM Blumenthal, H Li, S Subramaniam, PS Mishra-Kalyani, K He, H Zhao, J Yu, M Paciga, KB Goldberg, AE McKee, P Keegan, R Pazdur. FDA Approval Summary: pembrolizumab for treatment of metastatic non-small cell lung cancer: first-line therapy and beyond. Oncologist 2017; 22(11): 1392–1399 https://doi.org/10.1634/theoncologist.2017-0078
pmid: 28835513
8
Y Zhou, C Chen, X Zhang, S Fu, C Xue, Y Ma, W Fang, Y Yang, X Hou, Y Huang, H Zhao, S Hong, L Zhang. Immune-checkpoint inhibitor plus chemotherapy versus conventional chemotherapy for first-line treatment in advanced non-small cell lung carcinoma: a systematic review and meta-analysis. J Immunother Cancer 2018; 6(1): 155 https://doi.org/10.1186/s40425-018-0477-9
pmid: 30577837
JM Michot, C Bigenwald, S Champiat, M Collins, F Carbonnel, S Postel-Vinay, A Berdelou, A Varga, R Bahleda, A Hollebecque, C Massard, A Fuerea, V Ribrag, A Gazzah, JP Armand, N Amellal, E Angevin, N Noel, C Boutros, C Mateus, C Robert, JC Soria, A Marabelle, O Lambotte. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 2016; 54: 139–148 https://doi.org/10.1016/j.ejca.2015.11.016
pmid: 26765102
11
JA Thompson, BJ Schneider, J Brahmer, S Andrews, P Armand, S Bhatia, LE Budde, L Costa, M Davies, D Dunnington, MS Ernstoff, M Frigault, B Hoffner, CJ Hoimes, M Lacouture, F Locke, M Lunning, NA Mohindra, J Naidoo, AJ Olszanski, O Oluwole, SP Patel, S Reddy, M Ryder, B Santomasso, S Shofer, JA Sosman, M Wahidi, Y Wang, A Johnson-Chilla, JL Scavone. Management of immunotherapy-related toxicities, version 1.2019. J Natl Compr Canc Netw 2019; 17(3): 255–289 https://doi.org/10.6004/jnccn.2019.0013
pmid: 30865922
12
YC Kong, JC Flynn. Opportunistic autoimmune disorders potentiated by immune-checkpoint inhibitors anti-CTLA-4 and anti-PD-1. Front Immunol 2014; 5: 206 https://doi.org/10.3389/fimmu.2014.00206
pmid: 24904570
13
B El Osta, F Hu, R Sadek, R Chintalapally, SC Tang. Not all immune-checkpoint inhibitors are created equal: meta-analysis and systematic review of immune-related adverse events in cancer trials. Crit Rev Oncol Hematol 2017; 119: 1–12 https://doi.org/10.1016/j.critrevonc.2017.09.002
pmid: 29065979
14
LH Calabrese, C Calabrese, LC Cappelli. Rheumatic immune-related adverse events from cancer immunotherapy. Nat Rev Rheumatol 2018; 14(10): 569–579 https://doi.org/10.1038/s41584-018-0074-9
pmid: 30171203
15
I Puzanov, A Diab, K Abdallah, CO Bingham 3rd, C Brogdon, R Dadu, L Hamad, S Kim, ME Lacouture, NR LeBoeuf, D Lenihan, C Onofrei, V Shannon, R Sharma, AW Silk, D Skondra, ME Suarez-Almazor, Y Wang, K Wiley, HL Kaufman, MS Ernstoff; Society for Immunotherapy of Cancer Toxicity Management Working Group. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer 2017; 5(1): 95 https://doi.org/10.1186/s40425-017-0300-z
pmid: 29162153
16
LS Chang, R Barroso-Sousa, SM Tolaney, FS Hodi, UB Kaiser, L Min. Endocrine toxicity of cancer immunotherapy targeting immune checkpoints. Endocr Rev 2019; 40(1): 17–65
pmid: 30184160
P Arnaud-Coffin, D Maillet, HK Gan, JJ Stelmes, B You, S Dalle, J Péron. A systematic review of adverse events in randomized trials assessing immune checkpoint inhibitors. Int J Cancer 2019; 145(3): 639–648 https://doi.org/10.1002/ijc.32132
pmid: 30653255
20
JJ Moslehi, JE Salem, JA Sosman, B Lebrun-Vignes, DB Johnson. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet 2018; 391(10124): 933 https://doi.org/10.1016/S0140-6736(18)30533-6
pmid: 29536852
21
PF Wang, Y Chen, SY Song, TJ Wang, WJ Ji, SW Li, N Liu, CX Yan. Immune-related adverse events associated with anti-PD-1/PD-L1 treatment for malignancies: a meta-analysis. Front Pharmacol 2017; 8: 730 https://doi.org/10.3389/fphar.2017.00730
pmid: 29093678
22
A Bertrand, M Kostine, T Barnetche, ME Truchetet, T Schaeverbeke. Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis. BMC Med 2015; 13(1): 211 https://doi.org/10.1186/s12916-015-0455-8
pmid: 26337719
23
C Boutros, A Tarhini, E Routier, O Lambotte, FL Ladurie, F Carbonnel, H Izzeddine, A Marabelle, S Champiat, A Berdelou, E Lanoy, M Texier, C Libenciuc, AM Eggermont, JC Soria, C Mateus, C Robert. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol 2016; 13(8): 473–486 https://doi.org/10.1038/nrclinonc.2016.58
pmid: 27141885
24
L Khoja, D Day, T Wei-Wu Chen, LL Siu, AR Hansen. Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review. Ann Oncol 2017; 28(10): 2377–2385 https://doi.org/10.1093/annonc/mdx286
pmid: 28945858
25
J Naidoo, X Wang, KM Woo, T Iyriboz, D Halpenny, J Cunningham, JE Chaft, NH Segal, MK Callahan, AM Lesokhin, J Rosenberg, MH Voss, CM Rudin, H Rizvi, X Hou, K Rodriguez, M Albano, RA Gordon, C Leduc, N Rekhtman, B Harris, AM Menzies, AD Guminski, MS Carlino, BY Kong, JD Wolchok, MA Postow, GV Long, MD Hellmann. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clin Oncol 2017; 35(7): 709–717 https://doi.org/10.1200/JCO.2016.68.2005
pmid: 27646942
26
JD Wolchok, B Neyns, G Linette, S Negrier, J Lutzky, L Thomas, W Waterfield, D Schadendorf, M Smylie, T Guthrie Jr, JJ Grob, J Chesney, K Chin, K Chen, A Hoos, SJ O’Day, C Lebbé. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol 2010; 11(2): 155–164 https://doi.org/10.1016/S1470-2045(09)70334-1
pmid: 20004617
27
SL Topalian, M Sznol, DF McDermott, HM Kluger, RD Carvajal, WH Sharfman, JR Brahmer, DP Lawrence, MB Atkins, JD Powderly, PD Leming, EJ Lipson, I Puzanov, DC Smith, JM Taube, JM Wigginton, GD Kollia, A Gupta, DM Pardoll, JA Sosman, FS Hodi. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014; 32(10): 1020–1030 https://doi.org/10.1200/JCO.2013.53.0105
pmid: 24590637
28
DY Oh, J Cham, L Zhang, G Fong, SS Kwek, M Klinger, M Faham, L Fong. Immune toxicities elicted by CTLA-4 blockade in cancer patients are associated with early diversification of the T-cell repertoire. Cancer Res 2017; 77(6): 1322–1330 https://doi.org/10.1158/0008-5472.CAN-16-2324
pmid: 28031229
29
H Läubli, VH Koelzer, MS Matter, P Herzig, B Dolder Schlienger, MN Wiese, D Lardinois, KD Mertz, A Zippelius. The T cell repertoire in tumors overlaps with pulmonary inflammatory lesions in patients treated with checkpoint inhibitors. OncoImmunology 2018; 7(2): e1386362 https://doi.org/10.1080/2162402X.2017.1386362
pmid: 29308309
30
R Das, N Bar, M Ferreira, AM Newman, L Zhang, JK Bailur, A Bacchiocchi, H Kluger, W Wei, R Halaban, M Sznol, MV Dhodapkar, KM Dhodapkar. Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J Clin Invest 2018; 128(2): 715–720 https://doi.org/10.1172/JCI96798
pmid: 29309048
31
V Shahabi, D Berman, SD Chasalow, L Wang, Z Tsuchihashi, B Hu, L Panting, M Jure-Kunkel, RR Ji. Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events. J Transl Med 2013; 11(1): 75 https://doi.org/10.1186/1479-5876-11-75
pmid: 23521917
32
SY Lim, JH Lee, TN Gide, AM Menzies, A Guminski, MS Carlino, EJ Breen, JYH Yang, S Ghazanfar, RF Kefford, RA Scolyer, GV Long, H Rizos. Circulating cytokines predict immune-related toxicity in melanoma patients receiving anti-PD-1-based immunotherapy. Clin Cancer Res 2019; 25(5): 1557–1563 https://doi.org/10.1158/1078-0432.CCR-18-2795
pmid: 30409824
33
S Valpione, S Pasquali, LG Campana, L Piccin, S Mocellin, J Pigozzo, V Chiarion-Sileni. Sex and interleukin-6 are prognostic factors for autoimmune toxicity following treatment with anti-CTLA4 blockade. J Transl Med 2018; 16(1): 94 https://doi.org/10.1186/s12967-018-1467-x
pmid: 29642948
34
AA Tarhini, H Zahoor, Y Lin, U Malhotra, C Sander, LH Butterfield, JM Kirkwood. Baseline circulating IL-17 predicts toxicity while TGF-b1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma. J Immunother Cancer 2015; 3(1): 39 https://doi.org/10.1186/s40425-015-0081-1
pmid: 26380086
35
T Fujimura, Y Sato, K Tanita, Y Kambayashi, A Otsuka, Y Fujisawa, K Yoshino, S Matsushita, T Funakoshi, H Hata, Y Yamamoto, H Uchi, Y Nonomura, R Tanaka, M Aoki, K Imafuku, H Okuhira, S Furudate, T Hidaka, S Aiba. Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: a pilot study. Oncotarget 2018; 9(21): 15542–15551 https://doi.org/10.18632/oncotarget.24509
pmid: 29643991
36
O Hasan Ali , F Berner, D Bomze, M Fässler, S Diem, A Cozzio, M Jörger, M Früh, C Driessen, TL Lenz, L Flatz. Human leukocyte antigen variation is associated with adverse events of checkpoint inhibitors. Eur J Cancer 2019; 107:8–14 https://doi.org/10.1016/j.ejca.2018.11.009
pmid: 30529903
37
DY Wang, JE Salem, JV Cohen, S Chandra, C Menzer, F Ye, S Zhao, S Das, KE Beckermann, L Ha, WK Rathmell, KK Ancell, JM Balko, C Bowman, EJ Davis, DD Chism, L Horn, GV Long, MS Carlino, B Lebrun-Vignes, Z Eroglu, JC Hassel, AM Menzies, JA Sosman, RJ Sullivan, JJ Moslehi, DB Johnson. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol 2018; 4(12): 1721–1728 https://doi.org/10.1001/jamaoncol.2018.3923
pmid: 30242316
SG Downey, JA Klapper, FO Smith, JC Yang, RM Sherry, RE Royal, US Kammula, MS Hughes, TE Allen, CL Levy, M Yellin, G Nichol, DE White, SM Steinberg, SA Rosenberg. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin Cancer Res 2007; 13(22 Pt 1): 6681–6688 https://doi.org/10.1158/1078-0432.CCR-07-0187
pmid: 17982122
40
TZ Horvat, NG Adel, TO Dang, P Momtaz, MA Postow, MK Callahan, RD Carvajal, MA Dickson, SP D’Angelo, KM Woo, KS Panageas, JD Wolchok, PB Chapman. 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(28): 3193–3198 https://doi.org/10.1200/JCO.2015.60.8448
pmid: 26282644
41
JS Weber, S O’Day, W Urba, J Powderly, G Nichol, M Yellin, J Snively, E Hersh. Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol 2008; 26(36): 5950–5956 https://doi.org/10.1200/JCO.2008.16.1927
pmid: 19018089
42
DH Owen, L Wei, EM Bertino, T Edd, MA Villalona-Calero, K He, PG Shields, DP Carbone, GA Otterson. Incidence, risk factors, and effect on survival of immune-related adverse events in patients with non-small-cell lung cancer. Clin Lung Cancer 2018; 19(6): e893–e900 https://doi.org/10.1016/j.cllc.2018.08.008
pmid: 30197259
43
A Cortellini, R Chiari, B Ricciuti, G Metro, F Perrone, M Tiseo, M Bersanelli, P Bordi, D Santini, R Giusti, A Grassadonia, P Di Marino, N Tinari, M De Tursi, F Zoratto, E Veltri, F Malorgio, C Garufi, M Russano, C Anesi, T Zeppola, M Filetti, P Marchetti, R Berardi, S Rinaldi, M Tudini, RR Silva, A Pireddu, F Atzori, D Iacono, MR Migliorino, G Porzio, K Cannita, C Ficorella, S Buti. Correlations between the immune-related adverse events spectrum and efficacy of anti-PD1 immunotherapy in NSCLC patients. Clin Lung Cancer 2019; 20(4): 237–247.e1 https://doi.org/10.1016/j.cllc.2019.02.006
pmid: 30885550
44
Y Toi, S Sugawara, Y Kawashima, T Aiba, S Kawana, R Saito, K Tsurumi, K Suzuki, H Shimizu, J Sugisaka, H Ono, Y Domeki, K Terayama, A Nakamura, S Yamanda, Y Kimura, Y Honda. Association of immune-related adverse events with clinical benefit in patients with advanced non-small-cell lung cancer treated with nivolumab. Oncologist 2018; 23(11): 1358–1365 https://doi.org/10.1634/theoncologist.2017-0384
pmid: 29934411
45
J, Rogado JM Sánchez-Torres, N Romero-Laorden, AI Ballesteros, V Pacheco-Barcia, A Ramos-Leví , R Arranz, A, Lorenzo P, Gullón O, Donnay M Adrados, P Costas, J Aspa, A Alfranca, R Mondéjar, R. ColomerImmune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients. Eur J Cancer 2019; 109: 21–27 https://doi.org/10.1016/j.ejca.2018.10.014
pmid: 30682533
46
N Okada, H Kawazoe, K Takechi, Y Matsudate, R Utsunomiya, Y Zamami, M Goda, M Imanishi, M Chuma, N Hidaka, K Sayama, Y Kubo, A Tanaka, K Ishizawa. Association between immune-related adverse events and clinical efficacy in patients with melanoma treated with nivolumab: a multicenter retrospective study. Clin Ther 2019; 41(1): 59–67 https://doi.org/10.1016/j.clinthera.2018.11.004
pmid: 30528047
47
H Shafqat, T Gourdin, A Sion. Immune-related adverse events are linked with improved progression-free survival in patients receiving anti-PD-1/PD-L1 therapy. Semin Oncol 2018; 45(3): 156–163 https://doi.org/10.1053/j.seminoncol.2018.07.003
pmid: 30348532
48
M Kostine, L Rouxel, T Barnetche, R Veillon, F Martin, C Dutriaux, L Dousset, A Pham-Ledard, S Prey, M Beylot-Barry, A Daste, M Gross-Goupil, J Lallier, A Ravaud, E Forcade, B Bannwarth, ME Truchetet, C Richez, N Mehsen, T Schaeverbeke; FHU ACRONIM. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-clinical aspects and relationship with tumour response: a single-centre prospective cohort study. Ann Rheum Dis 2018; 77(3): 393–398 https://doi.org/10.1136/annrheumdis-2017-212257
pmid: 29146737
49
DFL Liew, JLY Leung, B Liu, J Cebon, AG Frauman, RRC Buchanan. Association of good oncological response to therapy with the development of rheumatic immune-related adverse events following PD-1 inhibitor therapy. Int J Rheum Dis 2019; 22(2): 297–302 https://doi.org/10.1111/1756-185X.13444
pmid: 30549256
50
HE Teulings, J Limpens, SN Jansen, AH Zwinderman, JB Reitsma, PI Spuls, RM Luiten. Vitiligo-like depigmentation in patients with stage III-IV melanoma receiving immunotherapy and its association with survival: a systematic review and meta-analysis. J Clin Oncol 2015; 33(7): 773–781 https://doi.org/10.1200/JCO.2014.57.4756
pmid: 25605840
51
C Hua, L Boussemart, C Mateus, E Routier, C Boutros, H Cazenave, R Viollet, M Thomas, S Roy, N Benannoune, G Tomasic, JC Soria, S Champiat, M Texier, E Lanoy, C Robert. Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab. JAMA Dermatol 2016; 152(1): 45–51 https://doi.org/10.1001/jamadermatol.2015.2707
pmid: 26501224
52
M Freeman-Keller, Y, Kim H Cronin, A Richards, G Gibney, JS Weber. Nivolumab in resected and unresectable metastatic melanoma: characteristics of immune-related adverse events and association with outcomes. Clin Cancer Res 2016; 22(4): 886–894 https://doi.org/10.1158/1078-0432.CCR-15-1136
pmid: 26446948
53
MA Postow, R Sidlow, MD Hellmann. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 2018; 378(2): 158–168 https://doi.org/10.1056/NEJMra1703481
pmid: 29320654
54
K Xing, B Gu, P Zhang, X Wu. Dexamethasone enhances programmed cell death 1 (PD-1) expression during T cell activation: an insight into the optimum application of glucocorticoids in anti-cancer therapy. BMC Immunol 2015; 16(1): 39 https://doi.org/10.1186/s12865-015-0103-2
pmid: 26112261
55
A Draghi, TH Borch, HD Radic, CA Chamberlain, A Gokuldass, IM Svane, M Donia. Differential effects of corticosteroids and anti-TNF on tumor-specific immune responses: implications for the management of irAEs. Int J Cancer 2019; 145(5): 1408–1413 https://doi.org/10.1002/ijc.32080
pmid: 30575963
56
K Margolin, MS Ernstoff, O Hamid, D Lawrence, D McDermott, I Puzanov, JD Wolchok, JI Clark, M Sznol, TF Logan, J Richards, T Michener, A Balogh, KN Heller, FS Hodi. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol 2012; 13(5): 459–465 https://doi.org/10.1016/S1470-2045(12)70090-6
pmid: 22456429
57
AT Faje, D Lawrence, K Flaherty, C Freedman, R Fadden, K Rubin, J Cohen, RJ Sullivan. High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma. Cancer 2018; 124(18): 3706–3714 https://doi.org/10.1002/cncr.31629
pmid: 29975414
58
K Esfahani, WH Miller Jr. Reversal of autoimmune toxicity and loss of tumor response by interleukin-17 blockade. N Engl J Med 2017; 376(20): 1989–1991 https://doi.org/10.1056/NEJMc1703047
pmid: 28514612
59
JS Weber, FS Hodi, JD Wolchok, SL Topalian, D Schadendorf, J Larkin, M Sznol, GV Long, H Li, IM Waxman, J Jiang, C Robert. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J Clin Oncol 2017; 35(7): 785–792 https://doi.org/10.1200/JCO.2015.66.1389
pmid: 28068177
A Garant, C Guilbault, T Ekmekjian, Z Greenwald, P Murgoi, T Vuong. Concomitant use of corticosteroids and immune checkpoint inhibitors in patients with hematologic or solid neoplasms: a systematic review. Crit Rev Oncol Hematol 2017; 120: 86–92 https://doi.org/10.1016/j.critrevonc.2017.10.009
pmid: 29198341
JR Brahmer, C Lacchetti, BJ Schneider, MB Atkins, KJ Brassil, JM Caterino, I Chau, MS Ernstoff, JM Gardner, P Ginex, S Hallmeyer, J Holter Chakrabarty, NB Leighl, JS Mammen, DF McDermott, A Naing, LJ Nastoupil, T Phillips, LD Porter, I Puzanov, CA Reichner, BD Santomasso, C Seigel, A Spira, ME Suarez-Almazor, Y Wang, JS Weber, JD Wolchok, JA Thompson; National Comprehensive Cancer Network. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2018; 36(17): 1714–1768 https://doi.org/10.1200/JCO.2017.77.6385
pmid: 29442540
64
JBAG Haanen, F Carbonnel, C Robert, KM Kerr, S Peters, J Larkin, K Jordan; ESMO Guidelines Committee. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; 28(suppl_4): iv119–iv142 https://doi.org/10.1093/annonc/mdx225
pmid: 28881921
65
SA Khan, SL Pruitt, L Xuan, DE Gerber. Prevalence of autoimmune disease among patients with lung cancer: implications for immunotherapy treatment options. JAMA Oncol 2016; 2(11): 1507–1508 https://doi.org/10.1001/jamaoncol.2016.2238
pmid: 27262099
66
DB Johnson, RJ Sullivan, PA Ott, MS Carlino, NI Khushalani, F Ye, A Guminski, I Puzanov, DP Lawrence, EI Buchbinder, T Mudigonda, K Spencer, C Bender, J Lee, HL Kaufman, AM Menzies, JC Hassel, JM Mehnert, JA Sosman, GV Long, JI Clark. Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncol 2016; 2(2): 234–240 https://doi.org/10.1001/jamaoncol.2015.4368
pmid: 26633184
67
AM Menzies, DB Johnson, S Ramanujam, VG Atkinson, ANM Wong, JJ Park, JL McQuade, AN Shoushtari, KK Tsai, Z Eroglu, O Klein, JC Hassel, JA Sosman, A Guminski, RJ Sullivan, A Ribas, MS Carlino, MA Davies, SK Sandhu, GV Long. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol 2017; 28(2): 368–376
pmid: 27687304
68
N Abdel-Wahab, M Shah, MA Lopez-Olivo, ME Suarez-Almazor. Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: a systematic review. Ann Intern Med 2018; 168(2): 121–130 https://doi.org/10.7326/M17-2073
pmid: 29297009
69
A Cortellini, S Buti, D Santini, F Perrone, R Giusti, M Tiseo, M Bersanelli, M Michiara, A Grassadonia, D Brocco, N Tinari, M De Tursi, F Zoratto, E Veltri, R Marconcini, F Malorgio, C Garufi, M Russano, C Anesi, T Zeppola, M Filetti, P Marchetti, A Botticelli, GC Antonini Cappellini, F De Galitiis, MG Vitale, R Sabbatini, S Bracarda, R Berardi, S Rinaldi, M Tudini, RR Silva, A Pireddu, F Atzori, R Chiari, B Ricciuti, D Iacono, MR Migliorino, A Rossi, G Porzio, K Cannita, V Ciciarelli, MC Fargnoli, PA Ascierto, C Ficorella. Clinical outcomes of patients with advanced cancer and pre-existing autoimmune diseases treated with anti-programmed death-1 immunotherapy: a real-world transverse study. Oncologist 2019; 24(6): e327–e337 https://doi.org/10.1634/theoncologist.2018-0618
pmid: 30796151
70
FX Danlos, AL Voisin, V Dyevre, JM Michot, E Routier, L Taillade, S Champiat, S Aspeslagh, J Haroche, L Albiges, C Massard, N Girard, S Dalle, B Besse, S Laghouati, JC Soria, C Mateus, C Robert, E Lanoy, A Marabelle, O Lambotte. Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease. Eur J Cancer 2018; 91: 21–29 https://doi.org/10.1016/j.ejca.2017.12.008
pmid: 29331748
71
DB Johnson, RJ Sullivan, AM Menzies. Immune checkpoint inhibitors in challenging populations. Cancer 2017; 123(11): 1904–1911 https://doi.org/10.1002/cncr.30642
pmid: 28241095
72
FC Santini, H Rizvi, AJ Plodkowski, A Ni, ME Lacouture, M Gambarin-Gelwan, O Wilkins, E Panora, DF Halpenny, NM Long, MG Kris, CM Rudin, JE Chaft, MD Hellmann. Safety and efficacy of re-treating with immunotherapy after immune-related adverse events in patients with NSCLC. Cancer Immunol Res 2018; 6(9): 1093–1099 https://doi.org/10.1158/2326-6066.CIR-17-0755
pmid: 29991499
73
A Simonaggio, JM Michot, AL Voisin, J Le Pavec, M Collins, A Lallart, G Cengizalp, A Vozy, A Laparra, A Varga, A Hollebecque, S Champiat, A Marabelle, C Massard, O Lambotte. Evaluation of readministration of immune checkpoint inhibitors after immune-related adverse events in patients with cancer. JAMA Oncol 2019; 5(9): 1310 https://doi.org/10.1001/jamaoncol.2019.1022
pmid: 31169866
74
MH Pollack, A Betof, H Dearden, K Rapazzo, I Valentine, AS Brohl, KK Ancell, GV Long, AM Menzies, Z Eroglu, DB Johnson, AN Shoushtari. Safety of resuming anti-PD-1 in patients with immune-related adverse events (irAEs) during combined anti-CTLA-4 and anti-PD1 in metastatic melanoma. Ann Oncol 2018; 29(1): 250–255 https://doi.org/10.1093/annonc/mdx642
pmid: 29045547