Immune Checkpoint Inhibitors in Transplantation-A Case Series and Comprehensive Review of Current Knowledge.
Aged
Female
Graft Rejection
/ immunology
Graft Survival
/ drug effects
Humans
Immune Checkpoint Inhibitors
/ adverse effects
Immunocompromised Host
Immunosuppressive Agents
/ adverse effects
Male
Middle Aged
Neoplasms
/ drug therapy
Organ Transplantation
/ adverse effects
Risk Assessment
Risk Factors
Treatment Outcome
Tumor Microenvironment
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
01 01 2021
01 01 2021
Historique:
pubmed:
2
5
2020
medline:
27
7
2021
entrez:
2
5
2020
Statut:
ppublish
Résumé
Cancer is a leading cause of morbidity and deaths in solid organ transplant recipients. In immunocompetent patients, cancer prognosis has been dramatically improved with the development of immune checkpoint inhibitors (ICI), as programmed cell death protein 1/programmed death-ligand 1 and cytotoxic T lymphocyte-associated antigen 4 inhibitors, that increase antitumor immune responses. ICI has been developed outside of the scope of transplantation because of the theoretical risk of graft rejection, which has later been confirmed by the publication of several cases and small series. The use of ICI became unavoidable for treating advanced cancers including in organ transplant patients, but their management in this setting remains highly challenging, as to date no strategy to adapt the immunosuppression and to prevent graft rejection has been defined. In this article, we report a monocentric series of 5 solid organ transplant recipients treated with ICI and provide a comprehensive review of current knowledge of ICI management in the setting of solid organ transplantation. Strategies warranted to increase knowledge through collecting more exhaustive data are also discussed.
Identifiants
pubmed: 32355121
pii: 00007890-202101000-00015
doi: 10.1097/TP.0000000000003292
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Immunosuppressive Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
67-78Informations de copyright
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
J.Z. received speaker fees from Bristol-Myers Squibb (BMS). J.D. reports travel accommodations (Pierre Fabre, Roche). C.L. received research grants or honoraria from Roche, BMS, MSD, GSK, Novartis, Amgen, and travel accommodations (Roche, BMS, MSD), outside the submitted work. The other authors declare no conflicts of interest.
Références
Grulich AE, van Leeuwen MT, Falster MO, et al. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370:59–67.
Vajdic CM, van Leeuwen MT. Cancer incidence and risk factors after solid organ transplantation. Int J Cancer. 2009;125:1747–1754.
Engels EA, Pfeiffer RM, Fraumeni JF Jr, et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA. 2011;306:1891–1901.
Acuna SA, Fernandes KA, Daly C, et al. Cancer mortality among recipients of solid-organ transplantation in Ontario, Canada. JAMA Oncol. 2016;2:463–469.
Tanaka K, Albin MJ, Yuan X, et al. PDL1 is required for peripheral transplantation tolerance and protection from chronic allograft rejection. J Immunol. 2007;179:5204–5210.
Riella LV, Watanabe T, Sage PT, et al. Essential role of PDL1 expression on nonhematopoietic donor cells in acquired tolerance to vascularized cardiac allografts. Am J Transplant. 2011;11:832–840.
Aguirre LE, Guzman ME, Lopes G, et al. Immune checkpoint inhibitors and the risk of allograft rejection: a comprehensive analysis on an emerging issue. Oncologist. 2019;24:394–401.
Wong K, Shen J, D’Ambruoso S, et al. Safety and efficacy of immune checkpoint inhibitors in patients with metastatic cancer post solid organ transplantation: a case report and review of the literature. Transplant Proc. 2019;51:3053–3058.
Barnett R, Barta VS, Jhaveri KD. Preserved renal-allograft function and the PD-1 pathway inhibitor nivolumab. N Engl J Med. 2017;376:191–192.
Friend BD, Venick RS, McDiarmid SV, et al. Fatal orthotopic liver transplant organ rejection induced by a checkpoint inhibitor in two patients with refractory, metastatic hepatocellular carcinoma. Pediatr Blood Cancer. 2017;64:12
Hurkmans DP, Verhoeven JGHP, de Leur K, et al. Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment. J Immunother Cancer. 2019;7:182
Lipson EJ, Bodell MA, Kraus ES, et al. Successful administration of ipilimumab to two kidney transplantation patients with metastatic melanoma. J Clin Oncol. 2014;32:e69–e71.
Morales RE, Shoushtari AN, Walsh MM, et al. Safety and efficacy of ipilimumab to treat advanced melanoma in the setting of liver transplantation. J Immunother Cancer. 2015;3:22
Alhamad T, Venkatachalam K, Linette GP, et al. Checkpoint inhibitors in kidney transplant recipients and the potential risk of rejection. Am J Transplant. 2016;16:1332–1333.
Boils CL, Aljadir DN, Cantafio AW. Use of the PD-1 pathway inhibitor nivolumab in a renal transplant patient with malignancy. Am J Transplant. 2016;16:2496–2497.
Gastman BR, Ernstoff MS. Tolerability of immune checkpoint inhibition cancer therapy in a cardiac transplant patient. Ann Oncol. 2016;27:2304–2305.
Herz S, Höfer T, Papapanagiotou M, et al. Checkpoint inhibitors in chronic kidney failure and an organ transplant recipient. Eur J Cancer. 2016;67:66–72.
Jose A, Yiannoullou P, Bhutani S, et al. Renal allograft failure after ipilimumab therapy for metastatic melanoma: a case report and review of the literature. Transplant Proc. 2016;48:3137–3141.
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;374:896–898.
Ong M, Ibrahim AM, Bourassa-Blanchette S, et al. Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. J Immunother Cancer. 2016;4:64
Ranganath HA, Panella TJ. Administration of ipilimumab to a liver transplant recipient with unresectable metastatic melanoma. J Immunother. 2015;38:211
Spain L, Higgins R, Gopalakrishnan K, et al. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Ann Oncol. 2016;27:1135–1137.
Tamain M, Garrouste C, Aguilera D, et al. Mixed acute kidney allograft rejection after an antiprogrammed cell death protein 1 antibody treatment for lung epidermoid carcinoma. Transpl Int. 2016;29:1247–1248.
Biondani P, De Martin E, Samuel D. Safety of an anti-PD-1 immune checkpoint inhibitor in a liver transplant recipient. Ann Oncol. 2018;29:286–287.
De Toni EN, Gerbes AL. Tapering of immunosuppression and sustained treatment with nivolumab in a liver transplant recipient. Gastroenterology. 2017;152:1631–1633.
Dueland S, Guren TK, Boberg KM, et al. Acute liver graft rejection after ipilimumab therapy. Ann Oncol. 2017;28:2619–2620.
Kittai AS, Oldham H, Cetnar J, et al. Immune checkpoint inhibitors in organ transplant patients. J Immunother. 2017;40:277–281.
Kwatra V, Karanth NV, Priyadarshana K, et al. Pembrolizumab for metastatic melanoma in a renal allograft recipient with subsequent graft rejection and treatment response failure: a case report. J Med Case Rep. 2017;11:73
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.
Varkaris A, Lewis DW, Nugent FW. Preserved liver transplant after PD-1 pathway inhibitor for hepatocellular carcinoma. Am J Gastroenterol. 2017;112:1895–1896.
Winkler JK, Gutzmer R, Bender C, 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;40:341–344.
Wu CK, Juang GD, Lai HC. Tumor regression and preservation of graft function after combination with anti-PD-1 immunotherapy without immunosuppressant titration. Ann Oncol. 2017;28:2895–2896.
Deltombe C, Garandeau C, Renaudin K, et al. Severe allograft rejection and autoimmune hemolytic anemia after anti-PD1 therapy in a kidney transplanted patient. Transplantation. 2017;101:e291
Gassmann D, Weiler S, Mertens JC, et al. Liver allograft failure after nivolumab treatment-a case report with systematic literature research. Transplant Direct. 2018;4:e376
Goldman JW, Abdalla B, Mendenhall MA, et al. PD 1 checkpoint inhibition in solid organ transplants: 2 sides of a coin - case report. BMC Nephrol. 2018;19:210
Grant MJ, DeVito N, Salama AKS. Checkpoint inhibitor use in two heart transplant patients with metastatic melanoma and review of high-risk populations. Melanoma Manag. 2018;5:MMT10
Qin R, Salama AK. Report of ipilimumab in a heart transplant patient with metastatic melanoma on tacrolimus. Melanoma Manag. 2015;2:311–314.
Kuo JC, Lilly LB, Hogg D. Immune checkpoint inhibitor therapy in a liver transplant recipient with a rare subtype of melanoma: a case report and literature review. Melanoma Res. 2018;28:61–64.
Rammohan A, Reddy MS, Farouk M, et al. Pembrolizumab for metastatic hepatocellular carcinoma following live donor liver transplantation: the silver bullet? Hepatology. 2018;67:1166–1168.
Schvartsman G, Perez K, Sood G, et al. Immune checkpoint inhibitor therapy in a liver transplant recipient with melanoma. Ann Intern Med. 2017;167:361–362.
Singh P, Visger Von J, Prosek J, et al. Preserved renal allograft function and successful treatment of metastatic Merkel cell cancer post nivolumab therapy. Transplantation. 2019;103:e52–e53.
Abdel-Wahab N, Safa H, Abudayyeh A, et al. Corrections to: checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature. J Immunother Cancer. 2019;7:158
Chen JA, Esteghamat N, Kim EJ, et al. PD-1 blockade in a liver transplant recipient with microsatellite unstable metastatic colorectal cancer and hepatic impairment. J Natl Compr Canc Netw. 2019;17:1026–1030.
Esfahani K, Al-Aubodah TA, Thebault P, et al. Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation. Nat Commun. 2019;10:4712
Lee BT, Horwich BH, Chopra S, et al. Checkpoint inhibitor-induced rejection of a liver allograft: a combination of acute T cell-mediated and antibody-mediated rejection. Liver Transpl. 2019;25:1845–1848.
Miller DM, Faulkner-Jones BE, Stone JR, et al. Complete pathologic response of metastatic cutaneous squamous cell carcinoma and allograft rejection after treatment with combination immune checkpoint blockade. JAAD Case Rep. 2017;3:412–415.
Sadaat M, Jang S. Complete tumor response to pembrolizumab and allograft preservation in renal allograft recipient on immunosuppressive therapy. J Oncol Pract. 2018;14:198–199.
Venkatachalam K, Malone AF, Heady B, et al. Poor outcomes with the use of checkpoint inhibitors in kidney transplant recipients. Transplantation. 2019;104:1041–1047.
Zhuang L, Mou HB, Yu LF, et al. Immune checkpoint inhibitor for hepatocellular carcinoma recurrence after liver transplantation. Hepatobiliary Pancreat Dis Int. 2020;19:91–93.
Lesouhaitier M, Dudreuilh C, Tamain M, et al. Checkpoint blockade after kidney transplantation. Eur J Cancer. 2018;96:111–114.
Fisher J, Zeitouni N, Fan W, et al. Immune checkpoint inhibitor therapy in solid organ transplant recipients: a patient-centered systematic review. J Am Acad Dermatol. 2020;82:1490–1500.
Smedman TM, Line PD, Guren TK, et al. Graft rejection after immune checkpoint inhibitor therapy in solid organ transplant recipients. Acta Oncol. 2018;57:1414–1418.
Babey H, Quéré G, Descourt R, et al. Immune-checkpoint inhibitors to treat cancers in specific immunocompromised populations: a critical review. Expert Rev Anticancer Ther. 2018;18:981–989.
d’Izarny-Gargas T, Durrbach A, Zaidan M. Efficacy and tolerance of immune checkpoint inhibitors in transplant patients with cancer: a systematic review. Am J Transplant. [Epub ahead of print. February 6, 2020]. doi: 10.1111/ajt.15811
doi: 10.1111/ajt.15811
Manohar S, Thongprayoon C, Cheungpasitporn W, et al. Systematic review of the safety of immune checkpoint inhibitors among kidney transplant patients. Kidney Int Rep. 2020;5:149–158.
Johnson DB, Sullivan RJ, Menzies AM. Immune checkpoint inhibitors in challenging populations. Cancer. 2017;123:1904–1911.
DeLeon TT, Salomao MA, Aqel BA, et al. Pilot evaluation of PD-1 inhibition in metastatic cancer patients with a history of liver transplantation: the Mayo Clinic experience. J Gastrointest Oncol. 2018;9:1054–1062.
Zehou O, Leibler C, Arnault JP, et al. Ipilimumab for the treatment of advanced melanoma in six kidney transplant patients. Am J Transplant. 2018;18:3065–3071.
Tio M, Rai R, Ezeoke OM, et al. Anti-PD-1/PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis B/C infection. Eur J Cancer. 2018;104:137–144.
Lefaucheur C, Loupy A, Vernerey D, et al. Antibody-mediated vascular rejection of kidney allografts: a population-based study. Lancet. 2013;381:313–319.
Loupy A, Lefaucheur C. Antibody-mediated rejection of solid-organ allografts. N Engl J Med. 2018;379:1150–1160.
Seethapathy H, Zhao S, Chute DF, et al. The incidence, causes, and risk factors of acute kidney injury in patients receiving immune checkpoint inhibitors. Clin J Am Soc Nephrol. 2019;14:1692–1700.
Murakami N, Motwani S, Riella LV. Renal complications of immune checkpoint blockade. Curr Probl Cancer. 2017;41:100–110.
Perazella MA, Sprangers B. AKI in patients receiving immune checkpoint inhibitors. Clin J Am Soc Nephrol. 2019;14:1077–1079.
Cortazar FB, Kibbelaar ZA, Glezerman IG, et al. Clinical features and outcomes of immune checkpoint inhibitor-associated AKI: a multicenter study. J Am Soc Nephrol. 2020;31:435–446.
Perazella MA, Shirali AC. Immune checkpoint inhibitor nephrotoxicity: what do we know and what should we do? Kidney Int. 2020;97:62–74.
Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016;17:1374–1385.
Nghiem PT, Bhatia S, Lipson EJ, et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med. 2016;374:2542–2552.
Lu S, Stein JE, Rimm DL, et al. Comparison of biomarker modalities for predicting response to PD-1/PD-L1 checkpoint blockade: a systematic review and meta-analysis. JAMA Oncol. 2019;5:1195–1204.
Knoll GA, Kokolo MB, Mallick R, et al. Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data. BMJ. 2014;349:g6679
Vajdic CM, McDonald SP, McCredie MR, et al. Cancer incidence before and after kidney transplantation. JAMA. 2006;296:2823–2831.
Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379:341–351.
Anglicheau D, Naesens M, Essig M, et al. Establishing biomarkers in transplant medicine: a critical review of current approaches. Transplantation. 2016;100:2024–2038.
Naesens M, Anglicheau D. Precision transplant medicine: biomarkers to the rescue. J Am Soc Nephrol. 2018;29:24–34.
Naesens M, Friedewald J, Mas V, et al. A practical guide to the clinical implementation of biomarkers for subclinical rejection following kidney transplantation. Transplantation. 2019;104:700–707.
Rabant M, Amrouche L, Lebreton X, et al. Urinary C-X-C motif chemokine 10 independently improves the noninvasive diagnosis of antibody-mediated kidney allograft rejection. J Am Soc Nephrol. 2015;26:2840–2851.
Rabant M, Amrouche L, Morin L, et al. Early low urinary CXCL9 and CXCL10 might predict immunological quiescence in clinically and histologically stable kidney recipients. Am J Transplant. 2016;16:1868–1881.
Walker LSK. PD-1 and CTLA4: two checkpoints, one pathway? SCI IMMUNOL. 2017;2:eaan3864
Kamphorst AO, Wieland A, Nasti T, et al. Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Science. 2017;355:1423–1427.
Tai X, Laethem FV, Sharpe AH, et al. Induction of autoimmune disease in CTLA-4−/− mice depends on a specific CD28 motif that is required for in vivo costimulation. Proc Natl Acad Sci U S A. 2007;104:13756–13761.
Sugiura D, Maruhashi T, Okazaki IM, et al. Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses. Science. 2019;364:558–566.
Wei SC, Sharma R, Anang NAS, et al. Negative co-stimulation constrains T cell differentiation by imposing boundaries on possible cell states. Immunity. 2019;50:1084–1098.e10.
Li W, Zheng XX, Kuhr CS, et al. CTLA4 engagement is required for induction of murine liver transplant spontaneous tolerance. Am J Transplant. 2005;5:978–986.
Judge TA, Wu Z, Zheng XG, et al. The role of CD80, CD86, and CTLA4 in alloimmune responses and the induction of long-term allograft survival. J Immunol. 1999;162:1947–1951.
Haspot F, Fehr T, Gibbons C, et al. Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway. Blood. 2008;112:2149–2155.
Lucas CL, Workman CJ, Beyaz S, et al. LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L. Blood. 2011;117:5532–5540.
Sage PT, Paterson AM, Lovitch SB, et al. The coinhibitory receptor CTLA-4 controls B cell responses by modulating T follicular helper, T follicular regulatory, and T regulatory cells. Immunity. 2014;41:1026–1039.
Vincenti F, Rostaing L, Grinyo J, et al. Belatacept and long-term outcomes in kidney transplantation. N Engl J Med. 2016;3744333–343.
Sanchez-Fueyo A, Markmann JF. Immune exhaustion and transplantation. Am J Transplant. 2016;16:1953–1957.
Hartigan CR, Sun H, Ford ML. Memory T-cell exhaustion and tolerance in transplantation. Immunol Rev. 2019;292:225–242.
Martinez GJ, Pereira RM, Äijö T, et al. The transcription factor NFAT promotes exhaustion of activated CD8 + T cells. Immunity. 2015;42:265–278.
Khan O, Giles JR, McDonald S, et al. TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion. Nature. 2019;571:211–218.
Scott AC, Dündar F, Zumbo P, et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature. 2019;571:270–274.
Morris H, DeWolf S, Robins H, et al. Tracking donor-reactive T cells: evidence for clonal deletion in tolerant kidney transplant patients. Sci Transl Med. 2015;7:272ra10
Zuber J, Shonts B, Lau S-P, et al. Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome. Sci Immunol. 2016;1:eaah3732
DeWolf S, Grinshpun B, Savage T, et al. Quantifying size and diversity of the human T cell alloresponse. JCI Insight. 2018;3:e121256
Szabo PA, Levitin HM, Miron M, et al. Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease. Nat Commun. 2019;10:4706
Wu H, Malone AF, Donnelly EL, et al. Single-cell transcriptomics of a human kidney allograft biopsy specimen defines a diverse inflammatory response. J Am Soc Nephrol. 2018;29:2069–2080.
Singh M, Al-Eryani G, Carswell S, et al. High-throughput targeted long-read single cell sequencing reveals the clonal and transcriptional landscape of lymphocytes. Nat Commun. 2019;10:3120
Dong H, Zhu G, Tamada K, et al. B7-H1 determines accumulation and deletion of intrahepatic CD8(+) T lymphocytes. Immunity. 2004;20:327–336.
Ono Y, Perez-Gutierrez A, Nakao T, et al. Graft-infiltrating PD-L1hi cross-dressed dendritic cells regulate antidonor T cell responses in mouse liver transplant tolerance. Hepatology. 2018;67:1499–1515.
Shi XL, Mancham S, Hansen BE, et al. Counter-regulation of rejection activity against human liver grafts by donor PD-L1 and recipient PD-1 interaction. J Hepatol. 2016;64:1274–1282.
Morita M, Fujino M, Jiang G, et al. PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft. Am J Transplant. 2010;10:40–46.
Starke A, Lindenmeyer MT, Segerer S, et al. Renal tubular PD-L1 (CD274) suppresses alloreactive human T-cell responses. Kidney Int. 2010;78:38–47.
Zuber J, Sykes M. Mechanisms of mixed chimerism-based transplant tolerance. Trends Immunol. 2017;38:829–843.
Snyder AG, Hubbard NW, Messmer MN, et al. Intratumoral activation of the necroptotic pathway components RIPK1 and RIPK3 potentiates antitumor immunity. Sci Immunol. 2019;4:eaaw2004
Kumar BV, Ma W, Miron M, et al. Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites. Cell Rep. 2017;20:2921–2934.
Mackay LK, Rahimpour A, Ma JZ, et al. The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin. Nat Immunol. 2013;14:1294–1301.
Benítez C, Londoño MC, Miquel R, et al. Prospective multicenter clinical trial of immunosuppressive drug withdrawal in stable adult liver transplant recipients. Hepatology. 2013;58:1824–1835.
Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12:492–499.
Blank CU, Haining WN, Held W, et al. Defining ‘T cell exhaustion’. Nat Rev Immunol. 2019;19:665–674.
Wang S, Campos J, Gallotta M, et al. Intratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8+ T cells. Proc Natl Acad Sci U S A. 2016;113:E7240–E7249.
Ribas A, Medina T, Kummar S, et al. SD-101 in combination with pembrolizumab in advanced melanoma: results of a phase Ib, multicenter study. Cancer Discov. 2018;8:1250–1257.