Immune-related adverse events associated with immune checkpoint blockade

New England Journal of Medicine

Volumn 378, Issue 2, 2018, Pages 158-168

  Postow, Michael A ^a   Sidlow, Robert ^a   Hellmann, Matthew D ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATEZOLIZUMAB; ATOVAQUONE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DURVALUMAB; GLUCOCORTICOID; INFLIXIMAB; IPILIMUMAB; NIVOLUMAB; PEMBROLIZUMAB; PENTAMIDINE; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; SULFAMETHOXAZOLE; TRIMETHOPRIM; IMMUNOLOGICAL ANTINEOPLASTIC AGENT; IMMUNOSUPPRESSIVE AGENT; MONOCLONAL ANTIBODY;

ANTINEOPLASTIC ACTIVITY; ANXIETY DISORDER; ARTICLE; CANCER IMMUNOTHERAPY; CANCER PATIENT; CANCER SURVIVAL; CLINICAL OUTCOME; COLITIS; COLORECTAL CANCER; CROHN DISEASE; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG SAFETY; GLAUCOMA; GRAFT VERSUS HOST REACTION; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HODGKIN DISEASE; HUMAN; HYPERGLYCEMIA; HYPOPHYSITIS; IMMUNOPATHOLOGY; IMMUNOSUPPRESSIVE TREATMENT; INFECTION RISK; LIVER CELL CARCINOMA; MELANOMA; MUSCLE WEAKNESS; NON SMALL CELL LUNG CANCER; OPPORTUNISTIC INFECTION; OSTEOPOROSIS; OVERALL SURVIVAL; PHYSICIAN; PNEUMOCYSTOSIS; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RENAL CELL CARCINOMA; SKIN TOXICITY; STOMACH CANCER; TRANSITIONAL CELL CARCINOMA; TREATMENT DURATION; ULCERATIVE COLITIS; CELL CYCLE CHECKPOINT; IMMUNOLOGY; IMMUNOTHERAPY; NEOPLASM; PHYSIOLOGY; PROCEDURES; T LYMPHOCYTE;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS, IMMUNOLOGICAL; CELL CYCLE CHECKPOINTS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; IMMUNOTHERAPY; NEOPLASMS; T-LYMPHOCYTES;

EID: 85040654063     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMra1703481     Document Type: Article

References (76)

1. Weber JS, Hodi FS, Wolchok JD, et al. Safety profile of nivolumab monotherapy: A pooled analysis of patients with advanced melanoma. J Clin Oncol 2017; 35: 785-92.
2. Krummel MF, Allison JP. CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J Exp Med 1996; 183: 2533- 40.
3. Dong H, Strome SE, Salomao DR, et al. Tumor-Associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat Med 2002; 8: 793-800.
4. Boussiotis VA. Molecular and biochemical aspects of the PD-1 checkpoint pathway. N Engl J Med 2016; 375: 1767-78.
5. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995; 3: 541-7.
6. Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 1995; 270: 985-8.
7. Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999; 11: 141-51.
8. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015; 372: 2521-32.
9. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015; 373: 23-34.
10. Khoja LDD, Wei-Wu Chen T, Siu LL, Hansen AR. Tumour-And class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: A systematic review. Ann Oncol 2017; 28: 2377-85.
11. Abdel-Rahman O, ElHalawani H, Fouad M. Risk of endocrine complications in cancer patients treated with immune check point inhibitors: A meta-Analysis. Future Oncol 2016; 12: 413-25.
12. Naidoo J, Wang X, Woo KM, et al. Pneumonitis in patients treated with antiprogrammed death-1/programmed death ligand 1 therapy. J Clin Oncol 2017; 35: 709-17.
13. Morganstein DL, Lai Z, Spain L, et al. Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma. Clin Endocrinol (Oxf) 2017; 86: 614-20.
14. Osorio JC, Ni A, Chaft JE, et al. Antibody- mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer. Ann Oncol 2017; 28: 583-9.
15. Iwama S, De Remigis A, Callahan MK, Slovin SF, Wolchok JD, Caturegli P. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med 2014; 6: 230ra45.
16. Caturegli P, Di Dalmazi G, Lombardi M, et al. Hypophysitis secondary to cytotoxic T-lymphocyte-Associated protein 4 blockade: insights into pathogenesis from an autopsy series. Am J Pathol 2016; 186: 3225-35.
17. Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 2016; 375: 1749-55.
18. Byrne EH, Fisher DE. Immune and molecular correlates in melanoma treated with immune checkpoint blockade. Cancer 2017; 123: S11: 2143-53.
19. Callahan M, et al. Evaluation of serum IL-17 levels during ipilimumab therapy: correlation with colitis. J Clin Oncol 2011; 29: Suppl:2505. abstract.
20. Harbour SN, Maynard CL, Zindl CL, Schoeb TR, Weaver CT. Th17 cells give rise to Th1 cells that are required for the pathogenesis of colitis. Proc Natl Acad Sci U S A 2015; 112: 7061-6.
21. Esfahani K, Miller WH Jr. Reversal of autoimmune toxicity and loss of tumor response by interleukin-17 blockade. N Engl J Med 2017; 376: 1989-91.
22. Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis - results of two phase 3 trials. N Engl J Med 2014; 371: 326-38.
23. Weber JS, Yang JC, Atkins MB, Disis ML. Toxicities of immunotherapy for the practitioner. J Clin Oncol 2015; 33: 2092-9.
24. Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immunerelated adverse effects of immune checkpoint inhibitors: A review. JAMA Oncol 2016; 2: 1346-53.
25. Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti- PD-1 antibodies alone and in combination. Nat Rev Clin Oncol 2016; 13: 473-86.
26. Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and followup. Ann Oncol 2017; 28: Suppl 4: iv119-iv142.
27. Yanai S, Nakamura S, Matsumoto T. Nivolumab-induced colitis treated by infliximab. Clin Gastroenterol Hepatol 2017; 15(4): E80-e81.
28. Bergqvist V, Hertervig E, Gedeon P, et al. Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis. Cancer Immunol Immunother 2017; 66: 581-92.
29. 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.
30. Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission, and long-Term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014; 32: 1020-30.
31. Renton AE, Pliner HA, Provenzano C, et al. A genome-wide association study of myasthenia gravis. JAMA Neurol 2015; 72: 396-404.
32. Dittmar M, Kahaly GJ. Immunoregulatory and susceptibility genes in thyroid and polyglandular autoimmunity. Thyroid 2005; 15: 239-50.
33. Yanagawa T, Hidaka Y, Guimaraes V, Soliman M, DeGroot LJ. CTLA-4 gene polymorphism associated with Graves' disease in a Caucasian population. J Clin Endocrinol Metab 1995; 80: 41-5.
34. Brewerton DA, Caffrey M, Nicholls A, Walters D, Oates JK, James DC. Reiter's disease and HL-A 27. Lancet 1973; 302: 996-8.
35. Wolchok JD, Weber JS, Hamid O, et al. Ipilimumab efficacy and safety in patients with advanced melanoma: A retrospective analysis of HLA subtype from four trials. Cancer Immun 2010; 10: 9.
36. Vetizou M, Pitt JM, Daillere R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015; 350: 1079-84.
37. Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti- PD-L1 efficacy. Science 2015; 350: 1084-9.
38. Chaput N, Lepage P, Coutzac C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol 2017; 28: 1368-79.
39. Dubin K, Callahan MK, Ren B, et al. Intestinal microbiome analyses identify melanoma patients at risk for checkpointblockade- induced colitis. Nat Commun 2016; 7: 10391.
40. Attia P, Phan GQ, Maker AV, 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.
41. Downey SG, Klapper JA, Smith FO, et al. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-Associated antigen-4 blockade. Clin Cancer Res 2007; 13: 6681-8.
42. Horvat TZ, Adel NG, Dang TO, 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.
43. Hua C, Boussemart L, Mateus C, et al. Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab. JAMA Dermatol 2016; 152: 45-51.
44. Teulings HE, Limpens J, Jansen SN, et al. Vitiligo-like depigmentation in patients with stage III-IV melanoma receiving immunotherapy and its association with survival: A systematic review and metaanalysis. J Clin Oncol 2015; 33: 773-81.
45. Burdick KH, Hawk WA. Vitiligo in a case of vaccinia virus-Treated melanoma. Cancer 1964; 17: 708-12.
46. Carli L, Tani C, Querci F, et al. Analysis of the prevalence of cataracts and glaucoma in systemic lupus erythematosus and evaluation of the rheumatologists' practice for the monitoring of glucocorticoid eye toxicity. Clin Rheumatol 2013; 32: 1071-3.
47. Huscher D, Thiele K, Gromnica-Ihle E, et al. Dose-related patterns of glucocorticoid- induced side effects. Ann Rheum Dis 2009; 68: 1119-24.
48. Kyi C, Hellmann MD, Wolchok JD, Chapman PB, Postow MA. Opportunistic infections in patients treated with immunotherapy for cancer. J Immunother Cancer 2014; 2: 19.
49. Arriola E, Wheater M, Krishnan R, Smart J, Foria V, Ottensmeier C. Immunosuppression for ipilimumab-related toxicity can cause pneumocystis pneumonia but spare antitumor immune control. Oncoimmunology 2015; 4(10): E1040218.
50. Uslu U, Agaimy A, Hundorfean G, Harrer T, Schuler G, Heinzerling L. Autoimmune colitis and subsequent CMV-induced hepatitis after treatment with ipilimumab. J Immunother 2015; 38: 212-5.
51. Del Castillo M, Romero FA, Arguello E, Kyi C, Postow MA, Redelman-Sidi G. The spectrum of serious infections among patients receiving immune checkpoint blockade for the treatment of melanoma. Clin Infect Dis 2016; 63: 1490-3.
52. National Comprehensive Cancer Network. Prevention and treatment of cancerrelated infections, version 1.2018, December 1, 2017 (http://www.nccn.org/professionals/physician-gls/pdf/infections.pdf).
53. Menzies AM, Johnson DB, Ramanujam S, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol 2017; 28: 368- 76.
54. Santini F, Rizvi H, Wilkins O, van Voorthuysen M, Panora E, Halpenny D, et al. Safety of retreatment with immunotherapy after immune-related toxicity in patients with lung cancers treated with anti-PD(L)-1 therapy. J Clin Oncol 2017; 35: Suppl: 2012. abstract.
55. Schadendorf D, Wolchok JD, Hodi FS, et al. Efficacy and safety outcomes in patients with advanced melanoma who discontinued treatment with nivolumab and ipilimumab because of adverse events: A pooled analysis of randomized phase II and III trials. J Clin Oncol 2017; 35: 3807-14.
56. Johnson DB, Sullivan RJ, Menzies AM. Immune checkpoint inhibitors in challenging populations. Cancer 2017; 123: 1904-11.
57. Johnson DB, Sullivan RJ, Ott PA, et al. Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncol 2016; 2: 234-40.
58. Spain L, Higgins R, Gopalakrishnan K, Turajlic S, Gore M, Larkin J. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Ann Oncol 2016; 27: 1135-7.
59. Morales RE, Shoushtari AN, Walsh MM, Grewal P, Lipson EJ, Carvajal RD. Safety and efficacy of ipilimumab to treat advanced melanoma in the setting of liver transplantation. J Immunother Cancer 2015; 3: 22.
60. Lipson EJ, Bagnasco SM, Moore J Jr, et al. Tumor regression and allograft rejection after administration of anti-PD-1. N Engl J Med 2016; 374: 896-8.
61. Owonikoko TK, Kumar M, Yang S, et al. Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: A case report. Cancer Immunol Immunother 2017; 66: 45-50.
62. Bashey A, Medina B, Corringham S, et al. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood 2009; 113: 1581-8.
63. Ding W, LaPlant BR, Call TG, et al. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood 2017; 129: 3419-27.
64. Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study. J Clin Oncol 2016; 34: 2698-704.
65. Younes A, Santoro A, Shipp M, et al. Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: A multicentre, multicohort, single-Arm phase 2 trial. Lancet Oncol 2016; 17: 1283-94.
66. El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017; 389: 2492-502.
67. Davar D, Wilson M, Pruckner C, Kirkwood JM. PD-1 blockade in advanced melanoma in patients with hepatitis C and/or HIV. Case Rep Oncol Med 2015; 2015: 737389.
68. Wightman F, Solomon A, Kumar SS, et al. Effect of ipilimumab on the HIV reser voir in an HIV-infected individual with metastatic melanoma. AIDS 2015; 29: 504-6.
69. Burke MM, Kluger HM, Golden M, Heller KN, Hoos A, Sznol M. Case report: Response to ipilimumab in a patient with HIV with metastatic melanoma. J Clin Oncol 2011; 29(32): E792-e794.
70. Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: A single-Arm, multicentre, phase 2 trial. Lancet 2017; 389: 67-76.
71. Kanz BA, Pollack MH, Johnpulle R, et al. Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction. J Immunother Cancer 2016; 4: 60.
72. Betof AS, Nipp RD, Giobbie-Hurder A, et al. Impact of age on outcomes with immunotherapy for patients with melanoma. Oncologist 2017; 22: 963-71.
73. Nishijima TF, Muss HB, Shachar SS, Moschos SJ. Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: A systematic review and meta-Analysis. Cancer Treat Rev 2016; 45: 30-7.
74. Johnpulle RA, Conry RM, Sosman JA, Puzanov I, Johnson DB. Responses to immune checkpoint inhibitors in nonagenarians. Oncoimmunology 2016; 5(11): E1234572.
75. Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; 375: 1823-33.
76. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015; 372: 320-30.