Immunotherapy before and after liver transplantation, where are we now?
Main Article Content
Abstract
Background: There is limited evidence on safety and efficacy on immunotherapy use before and after liver transplantation.
Methods: A literature review was performed to identify patients who received immunotherapy before and after liver transplantation. We reviewed the rejection rate and risk factors of rejection. In patients treated for hepatocellular carcinoma (HCC), the oncological outcomes were evaluated including response rate, progression-free survival and overall survival.
Results: We identified 97 patients from 41 publications. The rejection rate was 36% (n = 35), and graft loss occurred in 11 patients (11%). Forty-four patients received immunotherapy before undergoing a liver transplantation. Among them patients who experienced rejection were transplanted earlier following their last dose of immunotherapy, with a median time of 2.9 weeks compared to 8.3 weeks in patients without rejection (p<0.001). Fifty-three patients had a prior liver transplantation and subsequently received immunotherapy. Among them patients who developed acute rejection received immunotherapy earlier after transplantation, with a median duration of 2.9 years compared to 4.0 years in patients without rejection (p = 0.04). Graft Programmed death-ligand 1 (PD-L1) positivity was more frequent among patients with acute rejection (100% vs. 0%) (p=0.005). In patients treated for recurrent HCC, those with treatment response were patients who received treatment at a later interval from transplant (median time of 4.5 vs. 2.2 years, p=0.02).
Conclusions: Rejection risk remains the major obstacle to immunotherapy use for patients with liver transplant. Shorter interval between immunotherapy and transplant are associated with increased risk of acute rejection.
Article Details
How to Cite
AU, Kin Pan; CHOK, Kenneth Siu Ho.
Immunotherapy before and after liver transplantation, where are we now?.
Medical Research Archives, [S.l.], v. 12, n. 10, oct. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5692>. Date accessed: 15 nov. 2024.
doi: https://doi.org/10.18103/mra.v12i10.5692.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Au KP, Chok KSH. Immunotherapy after liver transplantation: Where are we now? World J Gastrointest Surg. 2021;13(10):1267. doi:10.4240/WJGS.V13.I10.1267
3. Au KP, Chok KSH. Multidisciplinary approach for post-liver transplant recurrence of hepatocellular carcinoma: A proposed management algorithm. World J Gastroenterol. 2018;24(45):5081-5094. doi:10.3748/wjg.v24.i45.5081
4. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 45:228-247. doi:10.1016/j.ejca.2008.10.026
5. Nordness MF, Hamel S, Godfrey CM, et al. Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient? Am J Transplant. 2020;20(3):879-883. doi:10.1111/AJT.15617
6. Schwacha-Eipper B, Minciuna I, Banz V, Dufour JF. Immunotherapy as a Downstaging Therapy for Liver Transplantation. Hepatology. 2020;72(4):1488-1490. doi:10.1002/HEP.31234
7. Chen GH, Wang G Bin, Huang F, et al. Pretransplant use of toripalimab for hepatocellular carcinoma resulting in fatal acute hepatic necrosis in the immediate postoperative period. Transpl Immunol. 2021;66. doi:10.1016/J.TRIM.2021.101386
8. Chen Z, Hong X, Wang T, et al. Prognosis after liver transplantation in patients treated with anti- PD-1 immunotherapy for advanced hepatocellular carcinoma: case series. Ann Palliat Med. 2021;10 (9):9354361-9359361. doi:10.21037/APM-21-999
9. Dehghan Y, Schnickel GT, Hosseini M, et al. Rescue liver re-transplantation after graft loss due to severe rejection in the setting of pre-transplant nivolumab therapy. Clin J Gastroenterol. 2021;14 (6):1718-1724. doi:10.1007/S12328-021-01521-4
10. Sogbe M, López-Guerra D, Blanco-Fernández G, Sangro B, Narváez-Rodriguez I. Durvalumab as a Successful Downstaging Therapy for Liver Transplantation in Hepatocellular Carcinoma: The Importance of a Washout Period. Transplantation. 2021;105(12):E398-E400. doi:10.1097/TP.0000000000003855
11. Tabrizian P, Florman SS, Schwartz ME. PD-1 inhibitor as bridge therapy to liver transplantation? Am J Transplant. 2021;21(5):1979-1980. doi:10.1111/AJT.16448
12. Aby ES, Lake JR. Immune Checkpoint Inhibitor Therapy Before Liver Transplantation—Case and Literature Review. Transplant Direct. 2022;8(4):E1304. doi:10.1097/TXD.0000000000001304
13. Kang E, Martinez M, Moisander-Joyce H, et al. Stable liver graft post anti-PD1 therapy as a bridge to transplantation in an adolescent with hepatocellular carcinoma. Pediatr Transplant. 2022; 26(3). doi:10.1111/PETR.14209
14. Schnickel GT, Fabbri K, Hosseini M, et al. Liver transplantation for hepatocellular carcinoma following checkpoint inhibitor therapy with nivolumab. Am J Transplant. 2022;22(6):1699-1704. doi:10.1111/AJT.16965
15. Wang T, Chen Z, Liu Y, et al. Neoadjuvant programmed cell death 1 inhibitor before liver transplantation for HCC is not associated with increased graft loss. Liver Transpl. 2023;29(6):598-606. doi:10.1097/LVT.0000000000000083
16. Wang K, Guo WX, Chen MS, et al. Multimodality Treatment for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Large-Scale, Multicenter, Propensity Mathching Score Analysis. Medicine (Baltimore). 2016;95(11) :e3015. doi:10.1097/MD.0000000000003015
17. De Toni EN, Gerbes AL. Tapering of Immunosuppression and Sustained Treatment With Nivolumab in a Liver Transplant Recipient. Gastroenterology. 2017;152(6):1631-1633. doi:10.1053/j.gastro.2017.01.063
18. Friend BD, Venick RS, McDiarmid S V., 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):e26682. doi:10.1002/pbc.26682
19. Varkaris A, Lewis DW, Nugent FW. Preserved Liver Transplant After PD-1 Pathway Inhibitor for Hepatocellular Carcinoma. Am J Gastroenterol. 2017;112(12):1895-1896. doi:10.1038/ajg.2017.387
20. 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;(suppl 4S). doi:10.21037/jgo.2018.07.05
21. Gomez P, Naim A, Zucker K, Wong M. A Case of Hepatocellular Carcinoma (HCC) Immunotherapy Inducing Liver Transplant Rejection. Am J Gastroenterol. 2018;113.
22. 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(8). doi:10.1097/TXD.0000000000000814
23. Nasr F, Al Ghoche A, Diab S, et al. Pembrolizumab Monother-Apy in Relapsed Hepatocellular Carcinoma Post Living Donor Liver Transplantation and Sorafenib. Vol 1.; 2018. https://www.elsevier.com/books/robbins-and-cotran-patho-. Accessed February 7, 2021.
24. Rammohan A, Reddy MS, Farouk M, Vargese J, Rela M. Pembrolizumab for metastatic hepatocellular carcinoma following live donor liver transplantation: The silver bullet? Hepatology. 2018;67(3):1166-1168. doi:10.1002/hep.29575
25. Kumar S. Nivolumab-Induced Severe Allograft Rejection in Recurrent Post-Transplant Hepatocellular Carcinoma. Am J Gastroenterol. 2019;114. doi:10.14309/01.ajg.0000598472.41771.5f
26. Amjad W, Kotiah S, Gupta A, Morris M, Liu L, Thuluvath PJ. Successful Treatment of Disseminated Hepatocellular Carcinoma After Liver Transplantation With Nivolumab. J Clin Exp Hepatol. 2020;10(2): 185-187. doi:10.1016/J.JCEH.2019.11.009
27. Anugwom C, Leventhal T. Nivolumab-Induced Autoimmune-Like Cholestatic Hepatitis in a Liver Transplant Recipient. ACG case reports J. 2020;7(7):e00416. doi:10.14309/CRJ.0000000000000416
28. Al Jarroudi O, Ulusakarya A, Almohamad W, Afqir S, Morere J-F. Anti-Programmed Cell Death Protein 1 (PD-1) Immunotherapy for Metastatic Hepatocellular Carcinoma After Liver Transplantation: A Report of Three Cases. Cureus. 2020;12(10). doi:10.7759/cureus.11150
29. Owoyemi I, Vaughan LE, Costello CM, et al. Clinical outcomes of solid organ transplant recipients with metastatic cancers who are treated with immune checkpoint inhibitors: A single-center analysis. Cancer. 2020;126(21):4780-4787. doi:10.1002/CNCR.33134
30. Ben Khaled N, Roessler D, Reiter FP, Seidensticker M, Guba M, De Toni EN. Extending the Use of Atezolizumab and Bevacizumab to a Liver Transplant Recipient: Need for a Posttransplant Registry. Liver Transpl. 2021;27(6):928-929. doi:10.1002/LT.26011
31. Rudolph M, Shah SA, Quillin R, et al. Immune checkpoint inhibitors in liver transplant: a case series. J Gastrointest Oncol. 2023;14(2):1141-1148. doi:10.21037/JGO-22-922/COIF)
32. Ranganath HA, Panella TJ. Administration of ipilimumab to a liver transplant recipient with unresectable metastatic melanoma. J Immunother. 2015;38(5):211. doi:10.1097/CJI.0000000000000077
33. 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(1):22. doi:10.1186/s40425-015-0066-0
34. 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(1): 286-287. doi:10.1093/annonc/mdx548
35. Dueland S, Guren TK, Boberg KM, et al. Acute liver graft rejection after ipilimumab therapy. Ann Oncol. 2017;28(10):2619-2620. doi:10.1093/annonc/mdx281
36. Schvartsman G, Perez K, Sood G, Katkhuda R, Tawbi H. Immune checkpoint inhibitor therapy in a liver transplant recipient with melanoma. Ann Intern Med. 2017;167(5):361-362. doi:10.7326/L17-0187
37. Kuo JC, Lilly LB, Hogg D. Immune checkpoint inhibitor therapy in a liver transplant recipient with a rare subtype of melanoma. Melanoma Res. 2018;28(1):61-64. doi:10.1097/CMR.0000000000000410
38. 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. doi:10.1016/j.ejca.2018.09.017
39. 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(9):1026-1030. doi:10.6004/JNCCN.2019.7328
40. Lee BT, Horwich BH, Chopra S, Ahearn A, Han HH. Checkpoint Inhibitor-Induced Rejection of a Liver Allograft: A Combination of Acute T Cell-Mediated and Antibody-Mediated Rejection. Liver Transpl. 2019;25(12):1845-1848. doi:10.1002/LT.25622
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