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
| العنوان: | 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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| المؤلفون: | Wan Yang, Pei Dong, Xia Liming, Jian-Chuan Xia, Xia Shangzhou, Ya Ding, Mengjia Song, Fangjian Zhou, Jingjing Li, Zhiling Zhang, Yue Huang, Jing Jing Zhao, De-Sheng Weng, Jia He, J. Yang, Shi-Ping Chen, Liu Heping, Ruiqing Peng, Junyi He, Yongqiang Li, Rongxing Huang, Zi-Qi Zhou, Jianxiong Zeng, Hao Chen, Qijing Wang, Chaopin Yang, Qiu-Zhong Pan, Jia-Mei Gu, Yan Tang, Yulong Han |
| المصدر: | Clinical & Translational Immunology Clinical & Translational Immunology, Vol 10, Iss 3, Pp n/a-n/a (2021) |
| بيانات النشر: | John Wiley and Sons Inc., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, lcsh:Immunologic diseases. Allergy, dendritic cells and cytokine‐induced killer cells immunotherapy, medicine.medical_specialty, Combination therapy, medicine.medical_treatment, Immunology, axitinib, Phases of clinical research, Pembrolizumab, 03 medical and health sciences, 0302 clinical medicine, Immunophenotyping, Renal cell carcinoma, Internal medicine, medicine, Immunology and Allergy, General Nursing, business.industry, advanced renal cell carcinoma, Immunotherapy, medicine.disease, Axitinib, 030104 developmental biology, 030220 oncology & carcinogenesis, Peripheral blood lymphocyte, Original Article, pembrolizumab, business, lcsh:RC581-607, medicine.drug |
| الوصف: | Objectives 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. Methods 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. Results 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. Conclusions 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. |
| اللغة: | English |
| تدمد: | 2050-0068 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e31a283234a237b5ba9f9c4690b15e13 http://europepmc.org/articles/PMC7927618 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e31a283234a237b5ba9f9c4690b15e13 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20500068 |
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