The efficacy and safety of the combination of axitinib and pembrolizumab-activated autologous DC-CIK cell immunotherapy for patients with advanced renal cell carcinoma: a phase 2 study.
The efficacy and safety of the combination of axitinib and pembrolizumab-activated autologous DC-CIK cell immunotherapy for patients with advanced renal cell carcinoma: a phase 2 study.
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阿西替尼和派姆单抗激活的自体 DC-CIK 细胞免疫疗法联合治疗晚期肾细胞癌的疗效和安全性：2 期研究
DOI：
10.1002/cti2.1257
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发表时间：
2021
影响因子：
5.8
通讯作者：
Xia JC
中科院分区：
文献类型：
--
作者：
Song MJ;Pan QZ;Ding Y;Zeng J;Dong P;Zhao JJ;Tang Y;Li J;Zhang Z;He J;Yang J;Huang Y;Peng R;Wang QJ;Gu JM;He J;Li YQ;Chen SP;Huang R;Zhou ZQ;Yang C;Han Y;Chen H;Liu H;Xia S;Wan Y;Weng DS;Xia L;Zhou FJ;Xia JC
Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab‐activated autologous dendritic cells–co‐cultured cytokine‐induced killer cells in patients with advanced RCC. All adult patients, including treatment‐naive or pretreated with VEGF‐targeted agents, were enrolled from May 2016 to March 2019. Patients received axitinib 5 mg twice daily and pembrolizumab‐activated dendritic cells–co‐cultured cytokine‐induced killer cells intravenously weekly for the first four cycles, every 2 weeks for the next four cycles, and every month thereafter. The 43 patients (22 untreated and 21 previously treated) showed a median progression‐free survival (mPFS) of 14.7 months (95% CI, 11.16–18.30). mPFS in treatment‐naive patients was 18.2 months, as compared with 14.4 months in pretreated patients (log‐rank P‐value = 0.07). Overall response rates were 25.6% (95% CI, 13.5–41.2%). Grade 3 or higher adverse events occurred in 5% of patients included hypertension (11.6%) and palmar‐plantar erythrodysesthesia (7.0%). Peripheral blood lymphocyte immunophenotype and serum cytokine profile analyses demonstrated increased antitumor immunity after combination treatment particularly in patients with a long‐term survival benefit, while those with a minimal survival benefit demonstrated an elevated proportion of peripheral CD8+TIM3+ T cells and lower serum‐level immunostimulatory cytokine profile. The combination therapy was active and well tolerated for treatment of advanced RCC, either as first‐ or second‐line treatment following other targeted agents. Changes in immunophenotype and serum cytokine profile may be used as prognostic biomarkers. This study demonstrated that the combination of axitinib plus pembrolizumab‐activated autologous DC‐cytokine‐induced killer cells contributed to encouraging clinical outcomes in patients with advanced renal cell carcinoma who were treatment‐naive or targeted agents‐pretreated. Such combination therapy led to superior antitumor immunity, including increased lymphocyte infiltration and cellular responses of CD8+ T cells, especially in patients who acquired long‐term survival benefit. An increased percentage of peripheral CD8+TIM3+ T cells and a lower serum‐level immunostimulatory cytokine profile were identified as a potential resistance mechanism to this combination therapy in patients with minimal survival benefit.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
15.9
作者：
Antonios, Joseph P.;Soto, Horacio;Prins, Robert M.
通讯作者：
Prins, Robert M.
影响因子：
45.3
作者：
McDermott, DF;Regan, MM;Atkins, MB
通讯作者：
Atkins, MB
影响因子：
45.3
作者：
Atkins, MB;Hidalgo, M;Sherman, ML
通讯作者：
Sherman, ML
影响因子：
3.7
作者：
Heine A;Held SA;Daecke SN;Riethausen K;Kotthoff P;Flores C;Kurts C;Brossart P
通讯作者：
Brossart P