Use of Immun Checkpoint Inhibitor Iplimumab in Renal Transplant Patents with Advanced Cancer: Is Risk/Benefit Ratio Dilemma?

Year 2020, Volume: 1 Issue: 2, 137 - 145, 30.09.2020

Merve Anapalı Eda Balkan

Abstract

End stage kidney disease is one of the most common diseases seen worldwide with high morbidity and mortality rate. Given current renal replacement therapies, the most effective method is renal transplantation compared to dialysis. Renal transplantation improves the patient's quality of life and complications related to dialysis are minimized. Long-term immunosuppressant therapy is applied to transplantation patients to ensure organ continuity by reducing the risk of acute rejection. Survival time after renal transplantation and increased use of immunosuppressive drugs increase the risk of developing metastatic tumors in these patients. It is predicted that immune checkpoint inhibitors applied to cancer patients can be used in patients with cancer development after transplantation. Ipilimumab is a cytotoxic T-lymhocyte-associated antigen 4 (CTLA-4) inhibitor developed specifically for use in metastatic melanoma patients and approved by the FDA in 2011. The effect of ipilimumab on allograft survival has been reported compared to other immune checkpoint inhibitors. Based on these data, we examined the renal case reports available in the literature to evaluate the relationship between cancer outcome and graft rejection.

Keywords

CTLA-4, ipilimumab, melanoma, PD-1, rejection, transplantation

References

• Referans1. Hart A, Smith JM, Skeans MA, Gustafson SK, Wilk AR, Robinson A, et al. OPTN/SRTR 2016 Annual Data Report: Kidney. Am J Transplant. 2018;18 Suppl 1:18-113.
• Referans2. Kim WR, Lake JR, Smith JM, Schladt DP, Skeans MA, Harper AM, et al. OPTN/SRTR 2016 Annual Data Report: Liver. Am J Transplant. 2018;18 Suppl 1:172-253.
• Referans3. Tsiatas M, Mountzios G, Curigliano G. Future perspectives in cancer immunotherapy. Ann Transl Med. 2016;4(14):273.
• Referans4. Munker S, De Toni EN. Use of checkpoint inhibitors in liver transplant recipients. United European Gastroenterol J. 2018;6(7):970-3.
• Referans5. Grinyo JM, Del Carmen Rial M, Alberu J, Steinberg SM, Manfro RC, Nainan G, et al. Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial. Am J Kidney Dis. 2017;69(5):587-94.
• Referans6. Tanaka K, Albin MJ, Yuan X, Yamaura K, Habicht A, Murayama T, et al. PDL1 is required for peripheral transplantation tolerance and protection from chronic allograft rejection. J Immunol. 2007;179(8):5204-10.
• Referans7. Riella LV, Watanabe T, Sage PT, Yang J, Yeung M, Azzi J, et al. Essential role of PDL1 expression on nonhematopoietic donor cells in acquired tolerance to vascularized cardiac allografts. Am J Transplant. 2011;11(4):832-40.
• Referans8. Lipson EJ, Bodell MA, Kraus ES, Sharfman WH. Successful administration of ipilimumab to two kidney transplantation patients with metastatic melanoma. J Clin Oncol. 2014;32(19):e69-71.
• Referans9. Doyle AM, Lechler RI, Turka LA. Organ transplantation: halfway through the first century. J Am Soc Nephrol. 2004;15(12):2965-71.
• Referans10. Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12(2):388-99.
• Referans11. Lindquist RR, Guttmann RD, Merrill JP, Dammin GJ. Human renal allografts. Interpretation of morphologic and immunohistochemical observations. Am J Pathol. 1968;53(5):851-81.
• Referans12. Kincaid-Smith P. Histological diagnosis of rejection of renal homografts in man. Lancet. 1967;2(7521):849-52.
• Referans13. Jeong HJ. Diagnosis of renal transplant rejection: Banff classification and beyond. Kidney Res Clin Pract. 2020;39(1):17-31.
• Referans14. Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008;8(4):753-60.
• Referans15. Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999;55(2):713-23.
• Referans16. Solez K, Colvin RB, Racusen LC, Sis B, Halloran PF, Birk PE, et al. Banff '05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN'). Am J Transplant. 2007;7(3):518-26.
• Referans17. Solez K, Axelsen RA, Benediktsson H, Burdick JF, Cohen AH, Colvin RB, et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int. 1993;44(2):411-22.
• Referans18. Scornik JC, Guerra G, Schold JD, Srinivas TR, Dragun D, Meier-Kriesche HU. Value of posttransplant antibody tests in the evaluation of patients with renal graft dysfunction. Am J Transplant. 2007;7(7):1808-14.
• Referans19. Terasaki PI. Humoral theory of transplantation. Am J Transplant. 2003;3(6):665-73.
• Referans20. Takemoto SK, Zeevi A, Feng S, Colvin RB, Jordan S, Kobashigawa J, et al. National conference to assess antibody-mediated rejection in solid organ transplantation. Am J Transplant. 2004;4(7):1033-41.
• Referans21. Racusen LC, Haas M. Antibody-mediated rejection in renal allografts: lessons from pathology. Clin J Am Soc Nephrol. 2006;1(3):415-20.
• Referans22. Colvin RB. Antibody-mediated renal allograft rejection: diagnosis and pathogenesis. J Am Soc Nephrol. 2007;18(4):1046-56.
• Referans23. Gloor J, Cosio F, Lager DJ, Stegall MD. The spectrum of antibody-mediated renal allograft injury: implications for treatment. Am J Transplant. 2008;8(7):1367-73.
• Referans24. Goldrath AW, Bevan MJ. Selecting and maintaining a diverse T-cell repertoire. Nature. 1999;402(6759):255-62.
• Referans25. Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008;224:166-82.
• Referans26. Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348(6230):56-61.
• Referans27. Buchbinder EI, Desai A. CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. Am J Clin Oncol. 2016;39(1):98-106.
• Referans28. Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol. 2001;19:565-94.
• Referans29. Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med. 1995;182(2):459-65.
• Referans30. Fallarino F, Fields PE, Gajewski TF. B7-1 engagement of cytotoxic T lymphocyte antigen 4 inhibits T cell activation in the absence of CD28. J Exp Med. 1998;188(1):205-10.
• Referans31. Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol. 2002;3(7):611-8.
• Referans32. Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, et al. Reversal of the TCR stop signal by CTLA-4. Science. 2006;313(5795):1972-5.
• Referans33. Linsey PS BJ, Greene J, et al. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity. 1996(4):535-43.
• Referans34. 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(6):2533-40.
• Referans35. Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N, et al. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med. 2000;192(2):303-10.
• Referans36. Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322(5899):271-5.
• Referans37. Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C, Schmidt EM, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011;332(6029):600-3.
• Referans38. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677-704.
• Referans39. Parry RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobayashi SV, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol. 2005;25(21):9543-53.
• Referans40. Bennett F, Luxenberg D, Ling V, Wang IM, Marquette K, Lowe D, et al. Program death-1 engagement upon TCR activation has distinct effects on costimulation and cytokine-driven proliferation: attenuation of ICOS, IL-4, and IL-21, but not CD28, IL-7, and IL-15 responses. J Immunol. 2003;170(2):711-8.
• Referans41. Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12(6):492-9.
• Referans42. Chen L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol. 2004;4(5):336-47.
• Referans43. Hino R, Kabashima K, Kato Y, Yagi H, Nakamura M, Honjo T, et al. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer. 2010;116(7):1757-66.
• Referans44. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20(19):5064-74.
• Referans45. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008;8(6):467-77.
• Referans46. Rozali EN, Hato SV, Robinson BW, Lake RA, Lesterhuis WJ. Programmed death ligand 2 in cancer-induced immune suppression. Clin Dev Immunol. 2012;2012:656340.
• Referans47. Huber S, Hoffmann R, Muskens F, Voehringer D. Alternatively activated macrophages inhibit T-cell proliferation by Stat6-dependent expression of PD-L2. Blood. 2010;116(17):3311-20.
• Referans48. Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007;27(1):111-22.
• Referans49. Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206(13):3015-29.
• Referans50. Moini M, Schilsky ML, Tichy EM. Review on immunosuppression in liver transplantation. World J Hepatol. 2015;7(10):1355-68.
• Referans51. Smedman TM, Line PD, Guren TK, Dueland S. Graft rejection after immune checkpoint inhibitor therapy in solid organ transplant recipients. Acta Oncol. 2018;57(10):1414-8.
• Referans52. Piselli P, Serraino D, Segoloni GP, Sandrini S, Piredda GB, Scolari MP, et al. Risk of de novo cancers after transplantation: results from a cohort of 7217 kidney transplant recipients, Italy 1997-2009. Eur J Cancer. 2013;49(2):336-44.
• Referans53. Zwald FO, Christenson LJ, Billingsley EM, Zeitouni NC, Ratner D, Bordeaux J, et al. Melanoma in solid organ transplant recipients. Am J Transplant. 2010;10(5):1297-304.
• Referans54. Sint Nicolaas J, de Jonge V, Steyerberg EW, Kuipers EJ, van Leerdam ME, Veldhuyzen-van Zanten SJ. Risk of colorectal carcinoma in post-liver transplant patients: a systematic review and meta-analysis. Am J Transplant. 2010;10(4):868-76.
• Referans55. Verran DJ, Mulhearn MH, Dilworth PJ, Balderson GA, Munn S, Chen JW, et al. Nature and outcomes of the increased incidence of colorectal malignancy after liver transplantation in Australasia. Med J Aust. 2013;199(9):610-2.
• Referans56. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373(19):1803-13.
• Referans57. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-54.
• Referans58. Hoffman W, Lakkis FG, Chalasani G. B Cells, Antibodies, and More. Clin J Am Soc Nephrol. 2016;11(1):137-54.
• Referans59. 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(6):1135-7.
• Referans60. Ong M, Ibrahim AM, Bourassa-Blanchette S, Canil C, Fairhead T, Knoll G. Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. J Immunother Cancer. 2016;4:64.
• Referans61. Alhamad T, Venkatachalam K, Linette GP, Brennan DC. Checkpoint Inhibitors in Kidney Transplant Recipients and the Potential Risk of Rejection. Am J Transplant. 2016;16(4):1332-3.
• Referans62. Herz S, Hofer T, Papapanagiotou M, Leyh JC, Meyenburg S, Schadendorf D, et al. Checkpoint inhibitors in chronic kidney failure and an organ transplant recipient. Eur J Cancer. 2016;67:66-72.
• Referans63. Peggs KS, Quezada SA, Chambers CA, Korman AJ, Allison JP. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med. 2009;206(8):1717-25.
• Referans64. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-23.
• Referans65. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517-26.
• Referans66. Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012;366(26):2517-9.
• Referans67. Lipson EJ, Bagnasco SM, Moore J, Jr., Jang S, Patel MJ, Zachary AA, et al. Tumor Regression and Allograft Rejection after Administration of Anti-PD-1. N Engl J Med. 2016;374(9):896-8.
• Referans68. Riella LV, Paterson AM, Sharpe AH, Chandraker A. Role of the PD-1 pathway in the immune response. Am J Transplant. 2012;12(10):2575-87.
• Referans69. Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13(5):459-65.
• Referans70. Pike R, Thomas N, Workman S, Ambrose L, Guzman D, Sivakumaran S, et al. PD1-Expressing T Cell Subsets Modify the Rejection Risk in Renal Transplant Patients. Front Immunol. 2016;7:126.
• Referans71. Winkler JK, Gutzmer R, Bender C, Lang N, Zeier M, Enk AH, et al. Safe Administration of An Anti-PD-1 Antibody to Kidney-transplant Patients: 2 Clinical Cases and Review of the Literature. J Immunother. 2017;40(9):341-4.
• Referans72. Acuna SA. Etiology of increased cancer incidence after solid organ transplantation. Transplant Rev (Orlando). 2018;32(4):218-24.
• Referans73. Ventola CL. Cancer Immunotherapy, Part 1: Current Strategies and Agents. P T. 2017;42(6):375-83.
• Referans74. McCoy KD, Le Gros G. The role of CTLA-4 in the regulation of T cell immune responses. Immunol Cell Biol. 1999;77(1):1-10.
• Referans75. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271(5256):1734-6.
• Referans76. 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(5):541-7.
• Referans77. Zhang T, Fresnay S, Welty E, Sangrampurkar N, Rybak E, Zhou H, et al. Selective CD28 blockade attenuates acute and chronic rejection of murine cardiac allografts in a CTLA-4-dependent manner. Am J Transplant. 2011;11(8):1599-609.
• Referans78. Lin H, Rathmell JC, Gray GS, Thompson CB, Leiden JM, Alegre ML. Cytotoxic T lymphocyte antigen 4 (CTLA4) blockade accelerates the acute rejection of cardiac allografts in CD28-deficient mice: CTLA4 can function independently of CD28. J Exp Med. 1998;188(1):199-204.
• Referans79. Jose A, Yiannoullou P, Bhutani S, Denley H, Morton M, Picton M, et al. Renal Allograft Failure After Ipilimumab Therapy for Metastatic Melanoma: A Case Report and Review of the Literature. Transplant Proc. 2016;48(9):3137-41.
• Referans80. Okano K NK, Horita S, et al. Effect of soluble form CTLA-4 on spontaneous IgA nephropathy in ddY mice. Nephrology. 2001.
• Referans81. 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.
• Referans82. Qin R, Salama AK. Report of ipilimumab in a heart transplant patient with metastatic melanoma on tacrolimus. Melanoma Manag. 2015;2(4):311-4.
• Referans83. Ranganath HA, Panella TJ. Administration of ipilimumab to a liver transplant recipient with unresectable metastatic melanoma. J Immunother. 2015;38(5):211.
• Referans84. Matin RN, Mesher D, Proby CM, McGregor JM, Bouwes Bavinck JN, del Marmol V, et al. Melanoma in organ transplant recipients: clinicopathological features and outcome in 100 cases. Am J Transplant. 2008;8(9):1891-900.
• Referans85. Zehou O, Leibler C, Arnault JP, Sayegh J, Montaudie H, Remy P, et al. Ipilimumab for the treatment of advanced melanoma in six kidney transplant patients. Am J Transplant. 2018;18(12):3065-71.
• Referans86. Curiel TJ. Tregs and rethinking cancer immunotherapy. J Clin Invest. 2007;117(5):1167-74.
• Referans87. Geissler EK. Post-transplantation malignancies: here today, gone tomorrow? Nat Rev Clin Oncol. 2015;12(12):705-17.
• Referans88. Lai HC, Lin JF, Hwang TIS, Liu YF, Yang AH, Wu CK. Programmed Cell Death 1 (PD-1) Inhibitors in Renal Transplant Patients with Advanced Cancer: A Double-Edged Sword? Int J Mol Sci. 2019;20(9).
• Referans89. Barnett R, Barta VS, Jhaveri KD. Preserved Renal-Allograft Function and the PD-1 Pathway Inhibitor Nivolumab. N Engl J Med. 2017;376(2):191-2.
• Referans90. Kang J, Demaria S, Formenti S. Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer. 2016;4:51.
• Referans91. Hiniker SM, Reddy SA, Maecker HT, Subrahmanyam PB, Rosenberg-Hasson Y, Swetter SM, et al. A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma. Int J Radiat Oncol Biol Phys. 2016;96(3):578-88.
• Referans92. Reynders K, Illidge T, Siva S, Chang JY, De Ruysscher D. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev. 2015;41(6):503-10.
• Referans93. Vanpouille-Box C, Formenti SC. Dual Transforming Growth Factor-beta and Programmed Death-1 Blockade: A Strategy for Immune-Excluded Tumors? Trends Immunol. 2018;39(6):435-7.
• Referans94. Luke JJ, Lemons JM, Karrison TG, Pitroda SP, Melotek JM, Zha Y, et al. Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors. J Clin Oncol. 2018;36(16):1611-8.