1932

Abstract

T cells have a central role in immune system balance. When activated, they may lead to autoimmune diseases. When too anergic, they contribute to infection spread and cancer proliferation. Immune checkpoint proteins regulate T cell function, including cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) and its ligand (PD-L1). These nodes of self-tolerance may be exploited pharmacologically to downregulate (CTLA-4 agonists) and activate [CTLA-4 and PD-1/PD-L1 antagonists, also called immune checkpoint inhibitors (ICIs)] the immune system.CTLA-4 agonists are used to treat rheumatologic immune disorders and graft rejection. CTLA-4, PD-1, and PD-L1 antagonists are approved for multiple cancer types and are being investigated for chronic viral infections. Notably, ICIs may be associated with immune-related adverse events (irAEs), which can be highly morbid or fatal. CTLA-4 agonism has been a promising method to reverse such life-threatening irAEs. Herein, we review the clinical pharmacology of these immune checkpoint agents with a focus on their interplay in human diseases.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-022820-093805
2021-01-06
2024-06-24
Loading full text...

Full text loading...

/deliver/fulltext/pharmtox/61/1/annurev-pharmtox-022820-093805.html?itemId=/content/journals/10.1146/annurev-pharmtox-022820-093805&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Pardoll DM. 2012. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12:4252–64
    [Google Scholar]
  2. 2. 
    Weiner HL. 1997. Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol. Today 18:7335–43
    [Google Scholar]
  3. 3. 
    Banan B, Xu Z, Gunasekaran M, Mohanakumar T 2013. Role of alloimmunity and autoimmunity in allograft rejection. Clin. Transpl. 2013:325–32
    [Google Scholar]
  4. 4. 
    Edgar JDM. 2008. T cell immunodeficiency. J. Clin. Pathol. 61:9988–93
    [Google Scholar]
  5. 5. 
    Chen L, Flies DB. 2013. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat. Rev. Immunol. 13:4227–42
    [Google Scholar]
  6. 6. 
    Chappert P, Schwartz RH. 2010. Induction of T cell anergy: integration of environmental cues and infectious tolerance. Curr. Opin. Immunol. 22:5552–59
    [Google Scholar]
  7. 7. 
    Grywalska E, Pasiarski M, Góźdź S, Roliński J 2018. Immune-checkpoint inhibitors for combating T-cell dysfunction in cancer. OncoTargets Ther. 11:6505–24
    [Google Scholar]
  8. 8. 
    Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA et al. 2010. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363:8711–23
    [Google Scholar]
  9. 9. 
    Makkouk A, Weiner G. 2015. Cancer immunotherapy and breaking immune tolerance—new approaches to an old challenge. Cancer Res 75:15–10
    [Google Scholar]
  10. 10. 
    Kaplon H, Reichert JM. 2019. Antibodies to watch in 2019. mAbs 11:2219–38
    [Google Scholar]
  11. 11. 
    Blair HA, Deeks ED. 2017. Abatacept: a review in rheumatoid arthritis. Drugs 77:111221–33
    [Google Scholar]
  12. 12. 
    Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S et al. 2016. Belatacept and long-term outcomes in kidney transplantation. N. Engl. J. Med. 374:4333–43
    [Google Scholar]
  13. 13. 
    Molloy ES, Calabrese LH. 2012. Progressive multifocal leukoencephalopathy associated with immunosuppressive therapy in rheumatic diseases: evolving role of biologic therapies. Arthritis Rheum 64:93043–51
    [Google Scholar]
  14. 14. 
    Wang DY, Salem J-E, Cohen JV, Chandra S, Menzer C et al. 2018. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol 4:121721–28
    [Google Scholar]
  15. 15. 
    Salem J-E, Allenbach Y, Vozy A, Brechot N, Johnson DB et al. 2019. Abatacept for severe immune checkpoint inhibitor-associated myocarditis. N. Engl. J. Med. 380:242377–79
    [Google Scholar]
  16. 16. 
    Kremer JM, Westhovens R, Leon M, Di Giorgio E, Alten R et al. 2003. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N. Engl. J. Med. 349:201907–15
    [Google Scholar]
  17. 17. 
    Priyadharshini B, Greiner DL, Brehm MA 2012. T cell activation and transplantation tolerance. Transplant. Rev. 26:3212–22
    [Google Scholar]
  18. 18. 
    Walker LSK, Sansom DM. 2011. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat. Rev. Immunol. 11:12852–63
    [Google Scholar]
  19. 19. 
    Rudd CE, Taylor A, Schneider H 2009. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol. Rev. 229:112–26
    [Google Scholar]
  20. 20. 
    Ishida Y, Agata Y, Shibahara K, Honjo T 1992. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 11:113887–95
    [Google Scholar]
  21. 21. 
    Brunet JF, Denizot F, Luciani MF, Roux-Dosseto M, Suzan M et al. 1987. A new member of the immunoglobulin superfamily–CTLA-4. Nature 328:6127267–70
    [Google Scholar]
  22. 22. 
    Dustin ML, Shaw AS. 1999. Costimulation: building an immunological synapse. Science 283:5402649–50
    [Google Scholar]
  23. 23. 
    Peixoto A, Evaristo C, Munitic I, Monteiro M, Charbit A et al. 2007. CD8 single-cell gene coexpression reveals three different effector types present at distinct phases of the immune response. J. Exp. Med. 204:51193–205
    [Google Scholar]
  24. 24. 
    Nagata S, Tanaka M. 2017. Programmed cell death and the immune system. Nat. Rev. Immunol. 17:5333–40
    [Google Scholar]
  25. 25. 
    Thompson CB, Allison JP. 1997. The emerging role of CTLA-4 as an immune attenuator. Immunity 7:4445–50
    [Google Scholar]
  26. 26. 
    Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C et al. 2011. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 332:6029600–3
    [Google Scholar]
  27. 27. 
    Ma Y, Lin B, Lin B, Hou S, Qian W et al. 2009. Pharmacokinetics of CTLA4Ig fusion protein in healthy volunteers and patients with rheumatoid arthritis. Acta Pharmacol. Sin. 30:3364–71
    [Google Scholar]
  28. 28. 
    Larsen CP, Pearson TC, Adams AB, Tso P, Shirasugi N et al. 2005. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am. J. Transplant. 5:3443–53
    [Google Scholar]
  29. 29. 
    Genovese MC, Becker J-C, Schiff M, Luggen M, Sherrer Y et al. 2005. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor α inhibition. N. Engl. J. Med. 353:111114–23
    [Google Scholar]
  30. 30. 
    Solomon DH, Kremer JM, Fisher M, Curtis JR, Furer V et al. 2014. Comparative cancer risk associated with methotrexate, other non-biologic and biologic disease-modifying anti-rheumatic drugs. Semin. Arthritis Rheum. 43:4489–97
    [Google Scholar]
  31. 31. 
    Montastruc F, Renoux C, Dell'Aniello S, Simon TA, Azoulay L et al. 2019. Abatacept initiation in rheumatoid arthritis and the risk of cancer: a population-based comparative cohort study. Rheumatology 58:4683–91
    [Google Scholar]
  32. 32. 
    de Germay S, Bagheri H, Despas F, Rousseau V, Montastruc F 2020. Abatacept in rheumatoid arthritis and the risk of cancer: a world observational post-marketing study. Rheumatology 59:9236067
    [Google Scholar]
  33. 33. 
    Rostaing L, Vincenti F, Grinyó J, Rice KM, Bresnahan B et al. 2013. Long-term belatacept exposure maintains efficacy and safety at 5 years: results from the long-term extension of the BENEFIT study. Am. J. Transplant. 13:112875–83
    [Google Scholar]
  34. 34. 
    Dekeyser M, de Goër de Herve M-G, Hendel-Chavez H, Labeyrie C, Adams D et al. 2017. Refractory T-cell anergy and rapidly fatal progressive multifocal leukoencephalopathy after prolonged CTLA4 therapy. Open Forum Infect. Dis. 4:2ofx100
    [Google Scholar]
  35. 35. 
    Martin ST, Powell JT, Patel M, Tsapepas D 2013. Risk of posttransplant lymphoproliferative disorder associated with use of belatacept. Am. J. Health-Syst. Pharm. 70:221977–83
    [Google Scholar]
  36. 36. 
    Bassil N, Rostaing L, Mengelle C, Kallab S, Esposito L et al. 2014. Prospective monitoring of cytomegalovirus, Epstein-Barr virus, BK virus, and JC virus infections on belatacept therapy after a kidney transplant. Exp. Clin. Transplant. 12:3212–19
    [Google Scholar]
  37. 37. 
    Harari A, Enders FB, Cellerai C, Bart P-A, Pantaleo G 2009. Distinct profiles of cytotoxic granules in memory CD8 T cells correlate with function, differentiation stage, and antigen exposure. J. Virol. 83:72862–71
    [Google Scholar]
  38. 38. 
    Duan J, Wang Y, Jiao S 2018. Checkpoint blockade‐based immunotherapy in the context of tumor microenvironment: opportunities and challenges. Cancer Med 7:94517–29
    [Google Scholar]
  39. 39. 
    de Coaña YP, Wolodarski M, Poschke I, Yoshimoto Y, Yang Y et al. 2017. Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory T cells in long-term survivors with advanced melanoma. Oncotarget 8:1321539–53
    [Google Scholar]
  40. 40. 
    Zhang Y, Du X, Liu M, Tang F, Zhang P et al. 2019. Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy. Cell Res 29:8609–27
    [Google Scholar]
  41. 41. 
    Du X, Tang F, Liu M, Su J, Zhang Y et al. 2018. A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy. Cell Res 28:4416–32
    [Google Scholar]
  42. 42. 
    Hui E, Cheung J, Zhu J, Su X, Taylor MJ et al. 2017. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science 355:63321428–33
    [Google Scholar]
  43. 43. 
    Baumeister SH, Freeman GJ, Dranoff G, Sharpe AH 2016. Coinhibitory pathways in immunotherapy for cancer. Annu. Rev. Immunol. 34:539–73
    [Google Scholar]
  44. 44. 
    Hassel JC, Heinzerling L, Aberle J, Bähr O, Eigentler TK et al. 2017. Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): evaluation and management of adverse drug reactions. Cancer Treat. Rev. 57:36–49
    [Google Scholar]
  45. 45. 
    Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM et al. 2017. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N. Engl. J. Med. 377:191824–35
    [Google Scholar]
  46. 46. 
    Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K et al. 2015. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med. 372:212006–17
    [Google Scholar]
  47. 47. 
    Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B et al. 2018. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N. Engl. J. Med. 378:141277–90
    [Google Scholar]
  48. 48. 
    Overman MJ, Lonardi S, Wong KYM, Lenz H-J, Gelsomino F et al. 2018. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J. Clin. Oncol. 36:8773–79
    [Google Scholar]
  49. 49. 
    Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R et al. 2019. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med. 380:121116–27
    [Google Scholar]
  50. 50. 
    Porichis F, Kaufmann DE. 2012. Role of PD-1 in HIV pathogenesis and as target for therapy. Curr. HIV/AIDS Rep. 9:181–90
    [Google Scholar]
  51. 51. 
    Cortese I, Muranski P, Enose-Akahata Y, Ha S-K, Smith B et al. 2019. Pembrolizumab treatment for progressive multifocal leukoencephalopathy. N. Engl. J. Med. 380:171597–605
    [Google Scholar]
  52. 52. 
    Walter O, Treiner E, Bonneville F, Mengelle C, Vergez F et al. 2019. Treatment of progressive multifocal leukoencephalopathy with nivolumab. N. Engl. J. Med. 380:171674–76
    [Google Scholar]
  53. 53. 
    Lobo ED, Hansen RJ, Balthasar JP 2004. Antibody pharmacokinetics and pharmacodynamics. J. Pharm. Sci. 93:112645–68
    [Google Scholar]
  54. 54. 
    Ovacik M, Lin K. 2018. Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development. Clin. Transl. Sci. 11:6540–52
    [Google Scholar]
  55. 55. 
    Dirks NL, Meibohm B. 2010. Population pharmacokinetics of therapeutic monoclonal antibodies. Clin. Pharmacokinet. 49:10633–59
    [Google Scholar]
  56. 56. 
    Romano E, Kusio-Kobialka M, Foukas PG, Baumgaertner P, Meyer C et al. 2015. Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients. PNAS 112:196140–45
    [Google Scholar]
  57. 57. 
    Davis PM, Abraham R, Xu L, Nadler SG, Suchard SJ 2007. Abatacept binds to the Fc receptor CD64 but does not mediate complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity. J. Rheumatol. 34:112204–10
    [Google Scholar]
  58. 58. 
    Morishita M, Peppas NA. 2006. Is the oral route possible for peptide and protein drug delivery. ? Drug Discov. Today 11:19–20905–10
    [Google Scholar]
  59. 59. 
    Renukuntla J, Vadlapudi AD, Patel A, Boddu SHS, Mitra AK 2013. Approaches for enhancing oral bioavailability of peptides and proteins. Int. J. Pharm. 447:1–275–93
    [Google Scholar]
  60. 60. 
    Marabelle A, Tselikas L, de Baere T, Houot R 2017. Intratumoral immunotherapy: using the tumor as the remedy. Ann. Oncol. 28:Suppl. 12xii33–43
    [Google Scholar]
  61. 61. 
    Zhao L, Ji P, Li Z, Roy P, Sahajwalla CG 2013. The antibody drug absorption following subcutaneous or intramuscular administration and its mathematical description by coupling physiologically based absorption process with the conventional compartment pharmacokinetic model. J. Clin. Pharmacol. 53:3314–25
    [Google Scholar]
  62. 62. 
    Ryman JT, Meibohm B. 2017. Pharmacokinetics of monoclonal antibodies. CPT Pharmacomet. Syst. Pharmacol. 6:9576–88
    [Google Scholar]
  63. 63. 
    Li X, Roy A, Murthy B 2019. Population pharmacokinetics and exposure‐response relationship of intravenous and subcutaneous abatacept in patients with rheumatoid arthritis. J. Clin. Pharmacol. 59:2245–57
    [Google Scholar]
  64. 64. 
    Mager DE, Jusko WJ. 2001. General pharmacokinetic model for drugs exhibiting target-mediated drug disposition. J. Pharmacokinet. Pharmacodyn. 28:6507–32
    [Google Scholar]
  65. 65. 
    Hayes JM, Frostell A, Cosgrave EFJ, Struwe WB, Potter O et al. 2014. Fc gamma receptor glycosylation modulates the binding of IgG glycoforms: a requirement for stable antibody interactions. J. Proteome Res. 13:125471–85
    [Google Scholar]
  66. 66. 
    Gessner JE, Heiken H, Tamm A, Schmidt RE 1998. The IgG Fc receptor family. Ann. Hematol. 76:6231–48
    [Google Scholar]
  67. 67. 
    Roopenian DC, Akilesh S. 2007. FcRn: The neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7:9715–25
    [Google Scholar]
  68. 68. 
    Kirsch AH, Lyko R, Nilsson L-G, Beck W, Amdahl M et al. 2017. Performance of hemodialysis with novel medium cut-off dialyzers. Nephrol. Dial. Transplant. 32:1165–72
    [Google Scholar]
  69. 69. 
    McKelvey EM, Yeoh HH, Schuster GA, Sharma B, Levin NW 1974. Immunoglobulin and dextran losses during peritoneal dialysis. Arch. Intern. Med. 134:2266–69
    [Google Scholar]
  70. 70. 
    Bouts AH, Davin JC, Krediet RT, van der Weel MB, Schröder CH et al. 2000. Immunoglobulins in chronic renal failure of childhood: effects of dialysis modalities. Kidney Int 58:2629–37
    [Google Scholar]
  71. 71. 
    Ascierto PA, Del Vecchio M, Robert C, Mackiewicz A, Chiarion-Sileni V et al. 2017. Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol 18:5611–22
    [Google Scholar]
  72. 72. 
    Feng Y, Roy A, Masson E, Chen T-T, Humphrey R, Weber JS 2013. Exposure-response relationships of the efficacy and safety of ipilimumab in patients with advanced melanoma. Clin. Cancer Res. 19:143977–86
    [Google Scholar]
  73. 73. 
    Moudgil A, Dharnidharka VR, Feig DI, Warshaw BL, Perera V et al. 2019. Phase I study of single-dose pharmacokinetics and pharmacodynamics of belatacept in adolescent kidney transplant recipients. Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg. 19:41218–23
    [Google Scholar]
  74. 74. 
    Centanni M, Moes DJAR, Trocóniz IF, Ciccolini J, van Hasselt JGC 2019. Clinical pharmacokinetics and pharmacodynamics of immune checkpoint inhibitors. Clin. Pharmacokinet. 58:7835–57
    [Google Scholar]
  75. 75. 
    Boyerinas B, Jochems C, Fantini M, Heery CR, Gulley JL et al. 2015. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol. Res. 3:101148–57
    [Google Scholar]
  76. 76. 
    Wilkins J, Brockhaus B, Wang S, Dai H, Neuteboom B et al. 2017. Population pharmacokinetic analysis of avelumab in different cancer types Poster presented at the 8th Annual American Conference on Pharmacometrics Fort Lauderdale, FL: October 15–18
    [Google Scholar]
  77. 77. 
    Hamuro L, Statkevich P, Bello A, Roy A, Bajaj G 2019. Nivolumab clearance is stationary in resected melanoma patients on adjuvant therapy: implications of disease status on time-varying clearance. Clin. Pharmacol. Ther. 106:51018–27
    [Google Scholar]
  78. 78. 
    Porporato PE. 2016. Understanding cachexia as a cancer metabolism syndrome. Oncogenesis 5:2e200
    [Google Scholar]
  79. 79. 
    Boswell CA, Tesar DB, Mukhyala K, Theil F-P, Fielder PJ, Khawli LA 2010. Effects of charge on antibody tissue distribution and pharmacokinetics. Bioconjug. Chem. 21:122153–63
    [Google Scholar]
  80. 80. 
    Rudnick SI, Adams GP. 2009. Affinity and avidity in antibody-based tumor targeting. Cancer Biother. Radiopharm. 24:2155–61
    [Google Scholar]
  81. 81. 
    Freshwater T, Kondic A, Ahamadi M, Li CH, de Greef R et al. 2017. Evaluation of dosing strategy for pembrolizumab for oncology indications. J. Immunother. Cancer 5:143
    [Google Scholar]
  82. 82. 
    Zhao X, Suryawanshi S, Hruska M, Feng Y, Wang X et al. 2017. Assessment of nivolumab benefit-risk profile of a 240-mg flat dose relative to a 3-mg/kg dosing regimen in patients with advanced tumors. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 28:82002–8
    [Google Scholar]
  83. 83. 
    Long GV, Tykodi SS, Schneider JG, Garbe C, Gravis G et al. 2018. Assessment of nivolumab exposure and clinical safety of 480mg every 4 weeks flat-dosing schedule in patients with cancer. Ann. Oncol. 29:112208–13
    [Google Scholar]
  84. 84. 
    Espinosa E, Márquez-Rodas I, Soria A, Berrocal A, Manzano JL et al. 2017. Predictive factors of response to immunotherapy—a review from the Spanish Melanoma Group (GEM). Ann. Transl. Med. 5:19389
    [Google Scholar]
  85. 85. 
    Feng Y, Masson E, Dai D, Parker SM, Berman D, Roy A 2014. Model-based clinical pharmacology profiling of ipilimumab in patients with advanced melanoma. Br. J. Clin. Pharmacol. 78:1106–17
    [Google Scholar]
  86. 86. 
    Bajaj G, Wang X, Agrawal S, Gupta M, Roy A, Feng Y 2017. Model-based population pharmacokinetic analysis of nivolumab in patients with solid tumors. CPT Pharmacomet. Syst. Pharmacol. 6:158–66
    [Google Scholar]
  87. 87. 
    Elassaiss-Schaap J, Rossenu S, Lindauer A, Kang SP, de Greef R et al. 2017. Using model-based “learn and confirm” to reveal the pharmacokinetics-pharmacodynamics relationship of pembrolizumab in the KEYNOTE-001 trial. CPT Pharmacomet. Syst. Pharmacol. 6:121–28
    [Google Scholar]
  88. 88. 
    Markham A, Duggan S. 2018. Cemiplimab: first global approval. Drugs 78:171841–46
    [Google Scholar]
  89. 89. 
    Postow MA, Sidlow R, Hellmann MD 2018. Immune-related adverse events associated with immune checkpoint blockade. N. Engl. J. Med. 378:2158–68
    [Google Scholar]
  90. 90. 
    Michot JM, Bigenwald C, Champiat S, Collins M, Carbonnel F et al. 2016. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur. J. Cancer 54:139–48
    [Google Scholar]
  91. 91. 
    Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC et al. 2012. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366:262443–54
    [Google Scholar]
  92. 92. 
    Brahmer JR, Tykodi SS, Chow LQM, Hwu W-J, Topalian SL et al. 2012. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 366:262455–65
    [Google Scholar]
  93. 93. 
    Puzanov I, Diab A, Abdallah K, Bingham CO, Brogdon C et al. 2017. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J. Immunother. Cancer 5:195
    [Google Scholar]
  94. 94. 
    Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S et al. 2017. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 28:Suppl. 4iv119–42
    [Google Scholar]
  95. 95. 
    Champiat S, Lambotte O, Barreau E, Belkhir R, Berdelou A et al. 2016. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann. Oncol. 27:4559–74
    [Google Scholar]
  96. 96. 
    Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J et al. 2016. Fulminant myocarditis with combination immune checkpoint blockade. N. Engl. J. Med. 375:181749–55
    [Google Scholar]
  97. 97. 
    Johnson DB, McDonnell WJ, Gonzalez-Ericsson PI, Al-Rohil RN, Mobley BC et al. 2019. A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis. Nat. Med. 25:81243–50
    [Google Scholar]
  98. 98. 
    Bomze D, Hasan Ali O, Bate A, Flatz L 2019. Association between immune-related adverse events during anti-PD-1 therapy and tumor mutational burden. JAMA Oncol 5:111633–35
    [Google Scholar]
  99. 99. 
    Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA et al. 2013. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 369:2122–33
    [Google Scholar]
  100. 100. 
    Salem J-E, Manouchehri A, Moey M, Lebrun-Vignes B, Bastarache L et al. 2018. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol 19:121579–89
    [Google Scholar]
  101. 101. 
    Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J et al. 2016. Fulminant myocarditis with combination immune checkpoint blockade. N. Engl. J. Med. 375:181749–55
    [Google Scholar]
  102. 102. 
    Champion SN, Stone JR. 2020. Immune checkpoint inhibitor associated myocarditis occurs in both high-grade and low-grade forms. Mod. Pathol. 33:199–108
    [Google Scholar]
  103. 103. 
    Suresh K, Naidoo J, Zhong Q, Xiong Y, Mammen J et al. 2019. The alveolar immune cell landscape is dysregulated in checkpoint inhibitor pneumonitis. J. Clin. Investig. 130:4305–15
    [Google Scholar]
  104. 104. 
    De Martin E, Michot J-M, Papouin B, Champiat S, Mateus C et al. 2018. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. J. Hepatol. 68:61181–90
    [Google Scholar]
  105. 105. 
    Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ et al. 2018. 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. 36:171714–68
    [Google Scholar]
  106. 106. 
    Faje AT, Lawrence D, Flaherty K, Freedman C, Fadden R et al. 2018. High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma. Cancer 124:183706–14
    [Google Scholar]
  107. 107. 
    Arbour KC, Mezquita L, Long N, Rizvi H, Auclin E et al. 2018. Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non-small-cell lung cancer. J. Clin. Oncol. 36:282872–78
    [Google Scholar]
  108. 108. 
    Esfahani K, Buhlaiga N, Thébault P, Lapointe R, Johnson NA, Miller WH 2019. Alemtuzumab for immune-related myocarditis due to PD-1 therapy. N. Engl. J. Med. 380:242375–76
    [Google Scholar]
  109. 109. 
    Sharma A, Bumerts P, Gomez-Navarro J, Pavlov D, Ribas A 2007. Clearance of monoclonal antibody (mAb) CP-675,206 by therapeutic plasma exchange (TPE) or plasmapheresis. J. Clin. Oncol. 25:Suppl. 1813515
    [Google Scholar]
  110. 110. 
    Guptill JT, Juel VC, Massey JM, Anderson AC, Chopra M et al. 2016. Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis. Autoimmunity 49:7472–79
    [Google Scholar]
  111. 111. 
    Ibrahim RB, Liu C, Cronin SM, Murphy BC, Cha R et al. 2007. Drug removal by plasmapheresis: an evidence-based review. Pharmacotherapy 27:111529–49
    [Google Scholar]
  112. 112. 
    Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J et al. 2010. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol. 28:193167–75
    [Google Scholar]
  113. 113. 
    Champion SN, Stone JR. 2020. Immune checkpoint inhibitor associated myocarditis occurs in both high-grade and low-grade forms. Mod. Pathol. 33:199–108
    [Google Scholar]
  114. 114. 
    Badell IR, Karadkhele GM, Vasanth P, Farris AB, Robertson JM, Larsen CP 2019. Abatacept as rescue immunosuppression after calcineurin inhibitor treatment failure in renal transplantation. Am. J. Transplant. 19:82342–49
    [Google Scholar]
  115. 115. 
    Saberianfar S, Nguyen LS, Manouchehri A, Lebrun-Vignes B, Moslehi JJ et al. 2020. Solid organ transplant rejection associated with immune-checkpoint inhibitors. Ann. Oncol. 31:4543–44
    [Google Scholar]
  116. 116. 
    van Brummelen EMJ, Ros W, Wolbink G, Beijnen JH, Schellens JHM 2016. Antidrug antibody formation in oncology: clinical relevance and challenges. Oncologist 21:101260–68
    [Google Scholar]
  117. 117. 
    Laurent S, Queirolo P, Boero S, Salvi S, Piccioli P et al. 2013. The engagement of CTLA-4 on primary melanoma cell lines induces antibody-dependent cellular cytotoxicity and TNF-α production. J. Transl. Med. 11:108
    [Google Scholar]
  118. 118. 
    Weber JS, O'Day S, Urba W, Powderly J, Nichol G et al. 2008. Phase I/II study of ipilimumab for patients with metastatic melanoma. J. Clin. Oncol. 26:365950–56
    [Google Scholar]
  119. 119. 
    Jutz S, Hennig A, Paster W, Asrak Ö, Dijanovic D et al. 2017. A cellular platform for the evaluation of immune checkpoint molecules. Oncotarget 8:3964892–906
    [Google Scholar]
  120. 120. 
    Wang C, Thudium KB, Han M, Wang X-T, Huang H et al. 2014. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol. Res. 2:9846–56
    [Google Scholar]
  121. 121. 
    Agrawal S, Statkevich P, Bajaj G, Feng Y, Saeger S et al. 2017. Evaluation of immunogenicity of nivolumab monotherapy and its clinical relevance in patients with metastatic solid tumors. J. Clin. Pharmacol. 57:3394–400
    [Google Scholar]
  122. 122. 
    Wang X, Ludwig EA, Passarell J, Bello A, Roy A, Hruska MW 2019. Population pharmacokinetics and exposure—safety analyses of nivolumab in patients with relapsed or refractory classical Hodgkin lymphoma. J. Clin. Pharmacol. 59:3364–73
    [Google Scholar]
  123. 123. 
    Nishino M, Giobbie-Hurder A, Manos MP, Bailey N, Buchbinder EI et al. 2017. Immune-related tumor response dynamics in melanoma patients treated with pembrolizumab: identifying markers for clinical outcome and treatment decisions. Clin. Cancer Res. 23:164671–79
    [Google Scholar]
  124. 124. 
    Shimizu T, Seto T, Hirai F, Takenoyama M, Nosaki K et al. 2016. Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors. Investig. New Drugs 34:347–54
    [Google Scholar]
  125. 125. 
    Stroh M, Winter H, Marchand M, Claret L, Eppler S et al. 2017. Clinical pharmacokinetics and pharmacodynamics of atezolizumab in metastatic urothelial carcinoma. Clin. Pharmacol. Ther. 102:2305–12
    [Google Scholar]
  126. 126. 
    Herbst RS, Soria J-C, Kowanetz M, Fine GD, Hamid O et al. 2014. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515:7528563–67
    [Google Scholar]
  127. 127. 
    Lee HT, Lee JY, Lim H, Lee SH, Moon YJ et al. 2017. Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab. Sci. Rep. 7:15532
    [Google Scholar]
  128. 128. 
    Donahue RN, Lepone LM, Grenga I, Jochems C, Fantini M et al. 2017. Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody. J. Immunother. Cancer. 5:20
    [Google Scholar]
  129. 129. 
    Vital EM, Emery P. 2006. Abatacept in the treatment of rheumatoid arthritis. Ther. Clin. Risk Manag. 2:4365–75
    [Google Scholar]
  130. 130. 
    Latek R, Fleener C, Lamian V, Kulbokas E, Davis PM et al. 2009. Assessment of belatacept-mediated costimulation blockade through evaluation of CD80/86-receptor saturation. Transplantation 87:6926–33
    [Google Scholar]
  131. 131. 
    Shen J, Townsend R, You X, Shen Y, Zhan P et al. 2014. Pharmacokinetics, pharmacodynamics, and immunogenicity of belatacept in adult kidney transplant recipients. Clin. Drug Investig. 34:2117–26
    [Google Scholar]
  132. 132. 
    Strohl WR. 2018. Current progress in innovative engineered antibodies. Protein Cell 9:186–120
    [Google Scholar]
  133. 133. 
    Bajaj G, Gupta M, Feng Y, Statkevich P, Roy A 2017. Exposure-response analysis of nivolumab in patients with previously treated or untreated advanced melanoma. J. Clin. Pharmacol. 57:121527–33
    [Google Scholar]
  134. 134. 
    Agrawal S, Feng Y, Roy A, Kollia G, Lestini B 2016. Nivolumab dose selection: challenges, opportunities, and lessons learned for cancer immunotherapy. J. Immunother. Cancer 4:72
    [Google Scholar]
  135. 135. 
    Chatterjee MS, Elassaiss-Schaap J, Lindauer A, Turner DC, Sostelly A et al. 2017. Population pharmacokinetic/pharmacodynamic modeling of tumor size dynamics in pembrolizumab-treated advanced melanoma. CPT Pharmacomet. Syst. Pharmacol. 6:129–39
    [Google Scholar]
  136. 136. 
    Chatterjee M, Turner DC, Felip E, Lena H, Cappuzzo F et al. 2016. Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer. Ann. Oncol. 27:71291–98
    [Google Scholar]
  137. 137. 
    Zhou Z, Shen J, Hong Y, Kaul S, Pfister M, Roy A 2012. Time-varying belatacept exposure and its relationship to efficacy/safety responses in kidney-transplant recipients. Clin. Pharmacol. Ther. 92:2251–57
    [Google Scholar]
  138. 138. 
    Keating MJ, Flinn I, Jain V, Binet J-L, Hillmen P et al. 2002. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 99:103554–61
    [Google Scholar]
  139. 139. 
    Tay RY, Blackley E, McLean C, Moore M, Bergin P et al. 2017. Successful use of equine anti-thymocyte globulin (ATGAM) for fulminant myocarditis secondary to nivolumab therapy. Br. J. Cancer 117:7921–24
    [Google Scholar]
  140. 140. 
    Vasudevan A, Gibson PR, van Langenberg DR 2017. Time to clinical response and remission for therapeutics in inflammatory bowel diseases: What should the clinician expect, what should patients be told. ? World J. Gastroenterol. 23:356385–402
    [Google Scholar]
  141. 141. 
    Hughes E, Scurr M, Campbell E, Jones E, Godkin A, Gallimore A 2018. T‐cell modulation by cyclophosphamide for tumour therapy. Immunology 154:162–68
    [Google Scholar]
  142. 142. 
    Jolles S, Sewell W, Misbah S 2005. Clinical uses of intravenous immunoglobulin. Clin. Exp. Immunol. 142:11–11
    [Google Scholar]
  143. 143. 
    Yong PF, D'Cruz DP. 2008. Mycophenolate mofetil in the treatment of lupus nephritis. Biol. Targets Ther. 2:2297–310
    [Google Scholar]
  144. 144. 
    Le RQ, Li L, Yuan W, Shord SS, Nie L et al. 2018. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. Oncologist 23:8943–47
    [Google Scholar]
  145. 145. 
    Emer JJ, Claire W. 2009. Rituximab. J. Clin. Aesthetic Dermatol. 2:529–37
    [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-022820-093805
Loading
/content/journals/10.1146/annurev-pharmtox-022820-093805
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error