A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant.
A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant.
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DOI：
10.1016/j.kint.2020.12.015
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发表时间：
2021-07
影响因子：
19.6
通讯作者：
Immune Checkpoint Inhibitors in Solid Organ Transplant Consortium
中科院分区：
文献类型：
--
作者：
Murakami N;Mulvaney P;Danesh M;Abudayyeh A;Diab A;Abdel-Wahab N;Abdelrahim M;Khairallah P;Shirazian S;Kukla A;Owoyemi IO;Alhamad T;Husami S;Menon M;Santeusanio A;Blosser CD;Zuniga SC;Soler MJ;Moreso F;Mithani Z;Ortiz-Melo D;Jaimes EA;Gutgarts V;Lum E;Danovitch GM;Cardarelli F;Drews RE;Bassil C;Swank JL;Westphal S;Mannon RB;Shirai K;Kitchlu A;Ong S;Machado SM;Mothi SS;Ott PA;Rahma O;Hodi FS;Sise ME;Gupta S;Leaf DE;Devoe CE;Wanchoo R;Nair VV;Schmults CD;Hanna GJ;Sprangers B;Riella LV;Jhaveri KD;Immune Checkpoint Inhibitors in Solid Organ Transplant Consortium
免疫检查点抑制剂（ICIs）广泛用于多种恶性肿瘤。然而，其在肾移植（KTx）患者中的安全性和有效性尚未明确。
我们对2010年1月至2020年5月期间69名接受免疫检查点抑制剂治疗的肾移植患者进行了一项多中心回顾性队列研究。在安全性方面，我们评估了急性移植物排斥反应的发生率、发生时间和危险因素。在有效性方面，我们评估了皮肤鳞状细胞癌（cSCC）和黑色素瘤（本队列中最常见的癌症）的客观缓解率（ORR）和总生存期（OS），并与未接受免疫检查点抑制剂治疗的、具有历史数据的、分期匹配的皮肤鳞状细胞癌（n = 23）和黑色素瘤（n = 14）肾移植患者进行了比较。
在接受免疫检查点抑制剂治疗后，69名患者中有29名（42%）发生了急性排斥反应，其中19名（65.5%）患者失去了移植物，而在未使用免疫检查点抑制剂的历史队列中，急性排斥反应发生率为5.4%。排斥反应率高于未使用免疫检查点抑制剂的历史队列（5.4%）。从开始使用免疫检查点抑制剂到发生排斥反应的中位时间为24天（四分位间距20 - 56天）。与较低排斥反应风险相关的因素是使用mTOR抑制剂（优势比[OR] 0.26；95%置信区间，0.09 - 0.72）和三联免疫抑制治疗（OR 0.67；95%置信区间，0.48 - 0.92）。皮肤鳞状细胞癌和黑色素瘤亚组的客观缓解率分别为36.4%和40%。在皮肤鳞状细胞癌亚组中，接受免疫检查点抑制剂治疗的患者总生存期更长（中位总生存期19.8个月对10.6个月；对数秩检验*p = 0.016），而在黑色素瘤亚组中，两组之间的总生存期无差异（中位总生存期13.5个月对11.4个月；对数秩检验p = 0.34）。
免疫检查点抑制剂与肾移植患者的高排斥反应风险相关，但可能会改善癌症预后。需要进行前瞻性研究以确定最佳的免疫抑制策略，从而改善患者的预后。
Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in kidney transplant (KTx) patients have not been defined. We conducted a multicenter retrospective cohort study of 69 KTx patients receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate (ORR) and overall survival (OS) were assessed in cutaneous squamous cell carcinoma (cSCC) and melanoma, the most common cancers in our cohort, and compared with historical, stage-matched KTx patients with cSCC (n=23) and melanoma (n=14) not receiving ICIs. Following ICI treatment, 29 out of 69 patients (42%) developed acute rejection, 19 of whom (65.5%) lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI historical cohort. The rejection rate was higher than the non-ICI historical cohort (5.4%). Median time from ICI initiation to rejection was 24 (IQR 20–56) days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio [OR] 0.26; 95%CI, 0.09–0.72) and triple-agent immunosuppression (OR 0.67; 95%CI, 0.48–0.92). ORR was 36.4% and 40% in the cSCC and melanoma subgroup, respectively. In cSCC subgroup, OS was longer in patients treated with ICIs (median OS 19.8 months vs. 10.6 months; log rank *p=0.016), whereas in the melanoma subgroup, OS did not differ between groups (median OS 13.5 months vs. 11.4 months; log rank p=0.34). ICIs were associated with a high risk of rejection in KTx patients but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.
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影响因子：
82.9
作者：
Fairfax BP;Taylor CA;Watson RA;Nassiri I;Danielli S;Fang H;Mahé EA;Cooper R;Woodcock V;Traill Z;Al-Mossawi MH;Knight JC;Klenerman P;Payne M;Middleton MR
通讯作者：
Middleton MR
影响因子：
10.9
作者：
Lanz, Joana;Bavinck, Jan Nico Bouwes;Hofbauer, Guenther F. L.
通讯作者：
Hofbauer, Guenther F. L.
影响因子：
158.5
作者：
Larkin, J.;Chiarion-Sileni, V.;Wolchok, J. D.
通讯作者：
Wolchok, J. D.
影响因子：
158.5
作者：
Robert, Caroline;Schachter, Jacob;Ribas, Antoni
通讯作者：
Ribas, Antoni
影响因子：
6
作者：
Seethapathy H;Zhao S;Strohbehn IA;Lee M;Chute DF;Bates H;Molina GE;Zubiri L;Gupta S;Motwani S;Leaf DE;Sullivan RJ;Rahma O;Blumenthal KG;Villani AC;Reynolds KL;Sise ME
通讯作者：
Sise ME