Systematic evaluation on PD-1 monoclonal antibody in the treatment of malignant tumor after solid organ transplantation
-
摘要:
目的 探讨实体器官移植(SOT)术后使用程序性细胞死亡受体-1(PD-1)单克隆抗体(单抗)治疗恶性肿瘤的有效性和安全性。 方法 检索7个数据库中的相关文献。收集54例SOT受者术后使用PD-1单抗治疗恶性肿瘤的案例,对使用PD-1单抗的SOT受者的临床效果及排斥反应情况进行分析。 结果 共纳入符合标准的文献32篇,共54例SOT受者。其中男43例,女11例,年龄为14~79岁。包括29例肾移植受者、19例肝移植受者、6例心脏移植受者。SOT受者使用的PD-1单抗药物类型包括28例使用派姆单抗、26例使用纳武单抗。PD-1单抗治疗SOT受者术后恶性肿瘤的总体缓解率为32%(17/54),疾病进展率44%(24/54),病死率为36%(19/54)。PD-1单抗治疗SOT受者术后恶性肿瘤后,排斥反应发生率为39%(21/54)。排斥反应与PD-1单抗药物类型无明显相关性(P > 0.05)。 结论 PD-1单抗能有效治疗SOT受者术后恶性肿瘤,治疗过程中可引发排斥反应,但排斥反应并不是导致受者死亡的最常见原因。 Abstract:Objective To investigate the efficacy and safety of programmed cell death protein-1 (PD-1) monoclonal antibody on the treatment of malignant tumor after solid organ transplantation (SOT). Methods The relevant literatures in 7 databases were searched. The data on 54 cases of recipients with malignant tumors treated with PD-1 monoclonal antibody after SOT were collected, and the clinical effects and rejection of SOT recipients treated with PD-1 monoclonal antibody were analyzed. Results Total 32 acceptable articles including 54 SOT recipients were incorporated, including 43 males and 11 females aged 14-79 years old. There are 29 renal transplant recipients, 19 liver transplant recipients and 6 heart transplant recipients. The types of PD-1 monoclonal antibody agent used by SOT recipients included pembrolizumab for 28 patients and nivolumab for 26 patients. The overall remission rate, disease progression rate and fatality rate of PD-1 monoclonal antibody for postoperative malignant tumors of SOT recipients were 32% (17/54), 44% (24/54) and 36% (19/54), respectively. After treatment with PD-1 monoclonal antibody for postoperative malignant tumors of SOT recipients, the incidence of rejection was 39% (21/54), indicating no significant correlation between rejection and type of PD-1 monoclonal antibody (P > 0.05). Conclusions PD-1 monoclonal antibody can effectively treat postoperative malignant tumors of SOT recipients, and may induce rejection during the treatment. But rejection is not the most common cause for death of recipients. -
表 1 纳入文献的基本信息
Table 1. Basic information of the included literatures
例序 年龄
(岁)性
别移植
物移植适应证 恶性肿瘤
类型PD-1单抗
类型其他抗
肿瘤治疗免疫抑制方案 排斥
反应临床
效果结局 1[7] 48 男 肝 原发性肝癌 肝癌 派姆单抗 否 FK506①+SRL② 否 NE 存活 2[8] 70 男 肝 原发性肝癌 肝癌 派姆单抗 是 FK506 否 PD 死亡 3[9] 57 男 肝 原发性肝癌 肝癌 派姆单抗 是 SRL+FK506+泼尼松 否 CR 存活 4[10] 35 男 肝 胆道闭锁 MM 派姆单抗 是 FK506 否 CR 存活 5[11] 63 女 肝 -④ MM 派姆单抗 否 环孢素 是 NE 死亡 6[12] 46 女 肝 药物中毒 MM 派姆单抗 否 SRL 是 PD 死亡 7[13] 62 女 肝 原发性肝癌 MM 派姆单抗 是 SRL+MMF③ 否 PR 存活 8[14] 55 男 肝 原发性肝癌 MM 派姆单抗 否 依维莫司+MMF 否 CR 存活 9[14] 63 男 肝 胆管细胞癌 MM 派姆单抗 否 泼尼松+MMF 是 NE 存活 10[14] 57 男 肝 原发性肝癌 肝癌 纳武单抗 是 FK506 否 PD 未知 11[14] 56 男 肝 原发性肝癌 肝癌 纳武单抗 是 MMF+SRL 否 PD 未知 12[14] 35 女 肝 原发性肝癌 肝癌 纳武单抗 是 FK506 否 PD 未知 13[14] 64 男 肝 原发性肝癌 肝癌 纳武单抗 是 FK506 否 NE 未知 14[14] 68 男 肝 原发性肝癌 肝癌 纳武单抗 是 SRL 是 PD 死亡 15[15] 53 女 肝 原发性肝癌 肝癌 纳武单抗 是 依维莫司+MMF 是 NE 死亡 16[16] 20 男 肝 原发性肝癌 肝癌 纳武单抗 是 SRL 是 NE 死亡 17[16] 14 男 肝 原发性肝癌 肝癌 纳武单抗 是 FK506 是 NE 死亡 18[17] 41 男 肝 原发性肝癌 肝癌 纳武单抗 是 FK506 否 PD 存活 19[18] 54 男 肝 肝硬化 NSCLC 纳武单抗 是 泼尼松+FK506+依维莫司 否 PD 死亡 20[19] 75 男 心 缺血性心肌病 MM 派姆单抗 是 FK506 否 PD 存活 21[20] 62 男 心 - MM 派姆单抗 是 FK506 否 PD 死亡 22[20] 67 男 心 缺血性心肌病 MM 派姆单抗 是 FK506+MMF 否 PD 死亡 23[12] 73 男 心 扩张型心肌病 MM 派姆单抗 否 FK506 否 PD 存活 24[21] 49 男 心 扩张型心肌病 cSCC 纳武单抗 是 泼尼松+FK506+SRL 是 NE 死亡 25[22] 72 女 心 风湿性心脏病 NSCLC 纳武单抗 是 MMF+环孢素 否 SD 存活 26[23] 61 男 肾 终末期肾病 尿路上皮癌 派姆单抗 是 MMF+FK506 否 PR 存活 27[24] 58 男 肾 移植肾排斥 MM 派姆单抗 是 环孢素 否 PD 死亡 28[25] 63 男 肾 肾硬化 cSCC 派姆单抗 是 SRL+泼尼松 否 CR 存活 29[26] 57 女 肾 - cSCC 派姆单抗 是 泼尼松 是 PR 存活 30[27] 58 男 肾 终末期肾病 MM 派姆单抗 否 硫唑嘌呤+依维莫司 是 PD 死亡 31[28] 68 男 肾 多囊肾 MM+cSCC 派姆单抗 是 泼尼松 是 NE 存活 32[12] 60 男 肾 高血压肾病 MM 派姆单抗 否 泼尼松 是 PD 死亡 33[12] 72 男 肾 多囊肾 MM 派姆单抗 否 泼尼松+环孢素+MMF 是 NE 存活 34[12] 71 男 肾 糖尿病肾病 MM 派姆单抗 否 泼尼松+SRL 否 PD 死亡 35[12] 66 男 肾 肾细胞癌 MM 派姆单抗 否 泼尼松+SRL+FK506 否 PD 死亡 36[12] 61 男 肾 IgA肾病 cSCC 派姆单抗 否 泼尼松+FK506 否 PR 存活 37[11] 65 男 肾 - MM 派姆单抗 是 泼尼松+MMF+依维莫司 否 PD 存活 38[11] 70 男 肾 - MM 派姆单抗 否 FK506+泼尼松 否 PD 存活 39[11] 75 男 肾 - MM 派姆单抗 否 泼尼松 否 PR 存活 40[11] 65 男 肾 - MM 派姆单抗 否 泼尼松+MMF+FK506 否 PD 存活 41[11] 48 男 肾 - MM 纳武单抗 否 泼尼松+FK506 是 PR 存活 42[12] 79 男 肾 终末期肾病 MM 纳武单抗 否 泼尼松+环孢素 否 PR 存活 43[22] 69 女 肾 局灶性节段性肾小球硬化 cSCC 纳武单抗 是 SRL+泼尼松 否 PR 存活 44[24] 60 女 肾 多囊肾 MM 纳武单抗 是 泼尼松龙+MMF 否 PD 死亡 45[29] 64 男 肾 终末期肾病 肺表皮样癌 纳武单抗 是 FK506+MMF 是 PD 存活 46[30] 48 男 肾 IgA肾病 MM 纳武单抗 是 泼尼松龙 是 PR 存活 47[31] 71 女 肾 多囊肾 默克尔细胞癌 纳武单抗 是 泼尼松 否 CR 存活 48[32] 63 女 肾 慢性肾功能衰竭 MM 纳武单抗 是 泼尼松 是 PR 存活 49[33] 72 男 肾 糖尿病肾病 cSCC 纳武单抗 是 停用 是 PR 死亡 50[34] 77 男 肾 糖尿病肾病 MM 纳武单抗 是 泼尼松+FK506 否 PD 存活 51[35] 50 男 肾 多囊肾 cSCC 纳武单抗 是 SRL+泼尼松 是 CR 存活 52[36] 73 男 肾 - MM 纳武单抗 否 依维莫司 是 PD 死亡 53[37] 74 男 肾 终末期肾病 NSCLC 纳武单抗 否 环孢素+泼尼松 是 NE 存活 54[38] 70 男 肾 肾细胞癌 十二指肠腺癌 纳武单抗 是 泼尼松+SRL 否 SD 存活 注:①FK506为他克莫司。
②SRL为西罗莫司。
③MMF为吗替麦考酚酯。
④-为资料不齐。 -
[1] YANG Y. Cancer immunotherapy: harnessing the immune system to battle cancer[J]. J Clin Invest, 2015, 125(9):3335-3337. DOI: 10.1172/JCI83871. [2] GUNTURI A, MCDERMOTT DF. Potential of new therapies like anti-PD1 in kidney cancer[J]. Curr Treat Options Oncol, 2014, 15(1):137-146. DOI: 10.1007/s11864-013-0268-y. [3] BACHY E, COIFFIER B. Anti-PD1 antibody: a new approach to treatment of lymphomas[J]. Lancet Oncol, 2014, 15(1):7-8. DOI: 10.1016/S1470-2045(13)70587-4. [4] 全诗翠, 胡佳, 刘畅, 等.免疫靶点PD-1/PD-L1的研究现状与应用进展[J].实用医学杂志, 2018, 34(14):2283-2286. DOI: 10.3969/j.issn.1006-5725.2018.14.001.QUAN SC, HU J, LIU C, et al. Research status and application progress of immunotarget PD-1/PD-L1[J]. J Pract Med, 2018, 34(14):2283-2286. DOI:10.3969/j.issn.1006-5725. 2018.14.001. [5] MAGGIORE U, PASCUAL J. The bad and the good news on cancer immunotherapy: implications for organ transplant recipients[J]. Adv Chronic Kidney Dis, 2016, 23(5):312-316. DOI: 10.1053/j.ackd.2016.08.002. [6] EISENHAUER EA, THERASSE P, BOGAERTS J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) [J]. Eur J Cancer, 2009, 45(2):228-247. DOI: 10.1016/j.ejca.2008.10.026. [7] 汪国营, 唐晖, 张英才, 等.程序性死亡受体(PD)-1单克隆抗体治疗肝癌肝移植术后复发诱发急性免疫性肝炎:附1例报告[J].器官移植, 2016, 7(1):44-47.DOI: 10.3969/j.issn.1674-7445.2016.01.008.WANG GY, TANG H, ZHANG YC, et al. Programmed death receptor(PD)-1 monoclonal antibody-induced acute immune hepatitis in the treatment of recurrent hepatocellular carcinoma after liver transplantation:a case report[J]. Organ Transplant, 2016, 7(1):44-47. DOI: 10.3969/j.issn.1674-7445.2016.01.008. [8] VARKARIS A, LEWIS DW, NUGENT FW. Preserved liver transplant after PD-1 pathway inhibitor for hepatocellular carcinoma[J]. Am J Gastroenterol, 2017, 112(12):1895-1896. DOI: 10.1038/ajg.2017.387. [9] RAMMOHAN A, REDDY MS, FAROUK M, et al. Pembrolizumab for metastatic hepatocellular carcinoma following live donor liver transplantation: the silver bullet? [J]. Hepatology, 2018, 67(3):1166-1168. DOI: 10.1002/hep.29575. [10] SCHVARTSMAN G, PEREZ K, SOOD G, et al. Immune checkpoint inhibitor therapy in a liver transplant recipient with melanoma[J]. Ann Intern Med, 2017, 167(5):361-362. DOI: 10.7326/L17-0187. [11] 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[J]. Eur J Cancer, 2018, 104:137-144. DOI: 10.1016/j.ejca.2018.09.017. [12] ABDEL-WAHAB N, SAFA H, ABUDAYYEH A, et al. Checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature[J]. J Immunother Cancer, 2019, 7(1):106. DOI: 10.1186/s40425-019-0585-1. [13] 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[J]. Melanoma Res, 2018, 28(1):61-64. DOI: 10.1097/CMR.0000000000000410. [14] 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]. J Gastrointest Oncol, 2018, 9(6):1054-1062. DOI: 10.21037/jgo.2018.07.05. [15] GASSMANN D, WEILER S, MERTENS JC, et al. Liver allograft failure after nivolumab treatment-a case report with systematic literature research[J]. Transplant Direct, 2018, 4(8):e376. DOI: 10.1097/TXD.0000000000000814. [16] 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[J]. Pediatr Blood Cancer, 2017, 64(12). DOI: 10.1002/pbc.26682. [17] DE TONI EN, GERBES AL. Tapering of immunosuppression and sustained treatment with nivolumab in a liver transplant recipient[J]. Gastroenterology, 2017, 152(6):1631-1633. DOI: 10.1053/j.gastro.2017.01.063. [18] BIONDANI P, DE MARTIN E, SAMUEL D. Safety of an anti-PD-1 immune checkpoint inhibitor in a liver transplant recipient[J]. Ann Oncol, 2018, 29(1):286-287. DOI: 10.1093/annonc/mdx548. [19] QIN R, SALAMA AK. Report of ipilimumab in a heart transplant patient with metastatic melanoma on tacrolimus[J]. Melanoma Manag, 2015, 2(4):311-314. DOI: 10.2217/mmt.15.27. [20] GRANT MJ, DEVITO N, SALAMA AKS. Checkpoint inhibitor use in two heart transplant patients with metastatic melanoma and review of high-risk populations[J]. Melanoma Manag, 2018, 5(4):MMT10. DOI: 10.2217/mmt-2018-0004. [21] 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[J]. Cancer Immunol Immunother, 2017, 66(1):45-50. DOI: 10.1007/s00262-016-1918-2. [22] KITTAI AS, OLDHAM H, CETNAR J, et al. Immune checkpoint inhibitors in organ transplant patients[J]. J Immunother, 2017, 40(7):277-281. DOI: 10.1097/CJI.0000000000000180. [23] WU CK, JUANG GD, LAI HC. Tumor regression and preservation of graft function after combination with anti-PD-1 immunotherapy without immunosuppressant titration[J]. Ann Oncol, 2017, 28(11):2895-2896. DOI: 10.1093/annonc/mdx409. [24] 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]. J Immunother, 2017, 40(9):341-344. DOI: 10.1097/CJI.0000000000000188. [25] SADAAT M, JANG S. Complete tumor response to pembrolizumab and allograft preservation in renal allograft recipient on immunosuppressive therapy[J]. J Oncol Pract, 2018, 14(3):198-199. DOI: 10.1200/JOP.2017.027326. [26] LIPSON EJ, BAGNASCO SM, MOORE J JR, et al. Tumor regression and allograft rejection after administration of anti-PD-1[J]. N Engl J Med, 2016, 374(9):896-898. DOI: 10.1056/NEJMc1509268. [27] 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]. J Med Case Rep, 2017, 11(1):73. DOI: 10.1186/s13256-017-1229-z. [28] ALHAMAD T, VENKATACHALAM K, LINETTE GP, et al. Checkpoint inhibitors in kidney transplant recipients and the potential risk of rejection[J]. Am J Transplant, 2016, 16(4):1332-1333. DOI: 10.1111/ajt.13711. [29] 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[J]. Transpl Int, 2016, 29(11):1247-1248. DOI: 10.1111/tri.12834. [30] SPAIN L, HIGGINS R, GOPALAKRISHNAN K, et al. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma[J]. Ann Oncol, 2016, 27(6):1135-1137. DOI: 10.1093/annonc/mdw130. [31] SINGH P, VISGER VON J, PROSEK J, et al. Preserved renal allograft function and successful treatment of metastatic merkel cell cancer post nivolumab therapy[J]. Transplantation, 2019, 103(2):e52-e53. DOI: 10.1097/TP.0000000000002502. [32] ONG M, IBRAHIM AM, BOURASSA-BLANCHETTE S, et al. Antitumor activity of nivolumab on hemodialysis after renal allograft rejection[J]. J Immunother Cancer, 2016, 4:64. doi: 10.1186/s40425-016-0171-8 [33] 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[J]. JAAD Case Rep, 2017, 3(5):412-415. DOI: 10.1016/j.jdcr.2017.06.005. [34] HERZ S, HÖFER T, PAPAPANAGIOTOU M, et al. Checkpoint inhibitors in chronic kidney failure and an organ transplant recipient[J]. Eur J Cancer, 2016, 67:66-72. DOI: 10.1016/j.ejca.2016.07.026. [35] GOLDMAN JW, ABDALLA B, MENDENHALL MA, et al. PD 1 checkpoint inhibition in solid organ transplants: 2 sides of a coin - case report[J]. BMC Nephrol, 2018, 19(1):210. DOI: 10.1186/s12882-018-1003-5. [36] DELTOMBE C, GARANDEAU C, RENAUDIN K, et al. Severe allograft rejection and autoimmune hemolytic anemia after anti-PD1 therapy in a kidney transplanted patient[J]. Transplantation, 2017, 101(9):e291. DOI: 10.1097/TP.0000000000001861. [37] BOILS CL, ALJADIR DN, CANTAFIO AW. Use of the PD-1 pathway inhibitor nivolumab in a renal transplant patient with malignancy[J]. Am J Transplant, 2016, 16(8):2496-2497. DOI: 10.1111/ajt.13786. [38] BARNETT R, BARTA VS, JHAVERI KD. Preserved renal-allograft function and the PD-1 pathway inhibitor nivolumab[J]. N Engl J Med, 2017, 376(2):191-192. DOI: 10.1056/NEJMc1614298. [39] 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]. J Hepatol, 2016, 64(6):1274-1282. DOI: 10.1016/j.jhep.2016.02.034. [40] TANAKA K, ALBIN MJ, YUAN X, et al. PDL1 is required for peripheral transplantation tolerance and protection from chronic allograft rejection[J]. J Immunol, 2007, 179(8):5204-5210. doi: 10.4049/jimmunol.179.8.5204 [41] THANGAVELU G, MURPHY KM, YAGITA H, et al. The role of co-inhibitory signals in spontaneous tolerance of weakly mismatched transplants[J]. Immunobiology, 2011, 216(8):918-924. DOI: 10.1016/j.imbio.2011.01.007. [42] AGUIRRE LE, GUZMAN ME, LOPES G, et al. Immune checkpoint inhibitors and the risk of allograft rejection: a comprehensive analysis on an emerging issue[J]. Oncologist, 2019, 24(3):394-401. DOI: 10.1634/theoncologist.2018-0195. [43] HODI FS, CHIARION-SILENI V, GONZALEZ R, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial[J]. Lancet Oncol, 2018, 19(11):1480-1492. DOI: 10.1016/S1470-2045(18)30700-9. [44] SCHACHTER J, RIBAS A, LONG GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006) [J]. Lancet, 2017, 390(10105):1853-1862. DOI: 10.1016/S0140-6736(17)31601-X.
计量
- 文章访问数: 275
- HTML全文浏览量: 120
- PDF下载量: 34
- 被引次数: 0