Liu Ming, Guan Wenhui, Xie Xiaohong, Li Zekun, Qiu Guihuan, Lin Xinqing, Xie Zhanhong, Zhang Jiexia, Qin Yinyin, Huang Zhenqian, Xu Xin, Zhou Chengzhi
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Clin Lung Cancer. 2025 May;26(3):e236-e241. doi: 10.1016/j.cllc.2024.12.013. Epub 2024 Dec 27.
Small cell lung cancer (SCLC) is initially highly sensitive to chemotherapy, which often leads to significant tumor reduction. However, the majority of patients eventually develop resistance, and the disease is further complicated by its "cold" tumor microenvironment, characterized by low tumor immunogenicity and limited CD8+ T cell infiltration. These factors contribute to the poor response to immunotherapy in many cases of extensive-stage SCLC (ES-SCLC). High-dose chemotherapy has shown potential in enhancing tumor cytoreduction, but its use is often limited by severe hematologic toxicity. Combining chemotherapy with immune checkpoint inhibitors (ICIs) can create a synergistic effect by promoting immunogenic cell death and enhancing immune activation. Autologous hematopoietic stem cell transplantation (auto-HSCT) provides a means to support hematopoietic recovery, mitigate chemotherapy-induced myelosuppression, and contribute to immune reconstitution. In this context, the integration of auto-HSCT with dose-intensified chemotherapy and ICIs aims to both protect the bone marrow and enhance antitumor immune responses, potentially overcoming resistance to immunotherapy in ES-SCLC.
A phase I, single-center, single-arm trial was designed to evaluate the safety and efficacy of auto-HSCT-supported dose-intensified chemotherapy combined with adebrelimab in treatment-naive ES-SCLC patients. Participants will receive induction chemotherapy followed by stem cell mobilization, apheresis, and cryopreservation. After successful mobilization, consolidation chemotherapy with stem cell reinfusion and granulocyte colony-stimulating factor (G-CSF) support will be performed. Maintenance therapy with adebrelimab continues until disease progression or unacceptable toxicity. Safety and efficacy data, including adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), will be analyzed.
The study aims to enhance treatment outcomes by overcoming resistance to immuno-chemotherapy and promoting immune reconstitution. The trial is ongoing at the First Affiliated Hospital of Guangzhou Medical University.
ClinicalTrials.gov Identifier: NCT06597513.
小细胞肺癌（SCLC）最初对化疗高度敏感，这通常会导致肿瘤显著缩小。然而，大多数患者最终会产生耐药性，并且该疾病因其“冷”肿瘤微环境而进一步复杂化，其特征是肿瘤免疫原性低和CD8 + T细胞浸润有限。这些因素导致许多广泛期小细胞肺癌（ES-SCLC）病例对免疫治疗反应不佳。高剂量化疗在增强肿瘤细胞减灭方面已显示出潜力，但其应用常常受到严重血液学毒性的限制。将化疗与免疫检查点抑制剂（ICI）联合使用可通过促进免疫原性细胞死亡和增强免疫激活产生协同效应。自体造血干细胞移植（auto-HSCT）提供了一种支持造血恢复、减轻化疗引起的骨髓抑制并有助于免疫重建的方法。在此背景下，将auto-HSCT与剂量强化化疗和ICI相结合旨在保护骨髓并增强抗肿瘤免疫反应，有可能克服ES-SCLC对免疫治疗的耐药性。
设计了一项I期单中心单臂试验，以评估auto-HSCT支持的剂量强化化疗联合阿得贝利单抗在初治ES-SCLC患者中的安全性和疗效。参与者将接受诱导化疗，随后进行干细胞动员、采集和冷冻保存。成功动员后，将进行干细胞回输和粒细胞集落刺激因子（G-CSF）支持的巩固化疗。继续使用阿得贝利单抗进行维持治疗，直至疾病进展或出现不可接受的毒性。将分析安全性和疗效数据，包括不良事件、客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。
该研究旨在通过克服对免疫化疗的耐药性和促进免疫重建来提高治疗效果。该试验正在广州医科大学附属第一医院进行。
ClinicalTrials.gov标识符：NCT06597513。
