PO.CL09.02 · 临床研究
belzutifan治疗Von Hippel-Lindau病相关肿瘤的安全性和疗效
Safety and efficacy of belzutifan for Von Hippel-Lindau disease-associated tumors
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：Von Hippel-Lindau（VHL）病是一种罕见的常染色体显性遗传综合征。VHL病患者终生存在发生透明细胞肾细胞癌（RCC）、胰腺神经内分泌肿瘤（pNET）以及中枢神经系统（CNS）血管母细胞瘤的风险。belzutifan是一种缺氧诱导因子-2alpha抑制剂，于2021年获FDA批准用于治疗成人VHL相关RCC、pNET或CNS血管母细胞瘤。2期数据显示，按RECIST v1.1标准评估的客观缓解率分别为49%、91%和30%。然而，真实世界的临床结局数据仍然有限。我们评估了belzutifan在真实世界队列中的安全性和疗效。
方法：我们对2016年1月至2024年12月期间在Johns Hopkins Hospital就诊、经基因或临床确诊为VHL并接受belzutifan治疗的成年患者（≥18岁）进行了回顾性分析。符合条件的参与者至少有一处VHL相关病灶，并在治疗后有可用的影像学资料。患者的人口学和临床数据从EMR中收集。使用CT或MRI评估基线和随访期间的肿瘤及囊肿特征。采用可评估病灶（包括<1 cm的病灶）最长径之和来评估肿瘤缓解情况。次要结局包括治疗持续时间、不良事件（AE）以及停药原因。
结果：共纳入14例患者（年龄均值±SD为36±14岁；71%为女性）。在10例有肾脏病灶的患者中，4/10（40%）在中位治疗持续时间18.5个月（范围12-27）内出现≥30%的缩小。全部3例（100%）有pNET的患者均出现≥30%的缩小，中位随访24.7个月（范围12-32）。在9例有CNS血管母细胞瘤的患者中，7/9（78%）在中位治疗持续时间18.1个月（范围7-28）内出现≥30%的缩小。最常见的AE为贫血（35%）、头晕（21%）和头痛（21%）。1例患者因贫血停药，另1例因计划妊娠停药。
结论：在这一VHL相关病灶患者的真实世界队列中，belzutifan在多种VHL相关肿瘤中显示出临床活性和良好的安全性特征。与2期数据相比，肾脏病灶的缓解率较低，而pNET和CNS血管母细胞瘤的缓解率较高。这些差异可能反映了基线影像学时间的差异、患者数量较少，或因保险问题或漏服剂量导致的偶发性治疗中断。这些发现支持继续在VHL病中使用belzutifan，并强调需要开展更大规模的研究以指导VHL相关肿瘤的长期管理。
查看英文原文 English abstract
Background : Von Hippel-Lindau (VHL) disease is a rare autosomal dominant hereditary syndrome. Patients with VHL disease have a lifelong risk of developing clear-cell renal cell carcinoma (RCC), pancreatic neuroendocrine tumors (pNET), and hemangioblastomas of the central nervous system (CNS). Belzutifan, a hypoxia-inducible factor-2alpha inhibitor, received FDA approval in 2021 for adults with VHL-associated RCC, pNET, or CNS hemangioblastomas. Phase 2 data demonstrated objective response rates of 49%, 91%, and 30% by RECIST v1.1, respectively. However, real-world clinical outcomes remain limited. We evaluated the safety and efficacy of belzutifan in a real-world cohort.
Methods : We performed a retrospective review of adult patients (≥18 years) at Johns Hopkins Hospital between January 2016 and December 2024 who were genetically or clinically confirmed to have VHL and received belzutifan treatment. Eligible participants had at least one VHL-associated lesion and an available imaging following therapy. Patient demographics and clinical data were collected from EMR. Tumor and cyst characteristics at baseline and during follow-up were evaluated using CT or MRI. The sum of the longest diameters of evaluable lesions-including lesions < 1 cm-was used to assess tumor response. Secondary outcomes included duration of therapy, adverse events (AEs), and reasons for treatment discontinuation.
Results : Fourteen patients were included (mean ± SD age, 36 ± 14 years; 71% female). Among 10 patients with kidney lesions, 4/10 (40%) had ≥30% decrease over a median treatment duration of 18.5 months (range 12 - 27). All 3 (100%) patients with pNET had a ≥30% decrease, with a median follow-up of 24.7 months (range 12-32). Among 9 patients with CNS hemangioblastomas, 7/9 (78%) had ≥30% decrease over a median treatment duration of 18.1 months (range 7-28). The most common AEs were anemia (35%), dizziness (21%), and headache (21%). One patient discontinued treatment due to anemia, and another due to pregnancy planning.
Conclusion : In this real-world cohort of patients with VHL-associated lesions, belzutifan demonstrated clinical activity and a favorable safety profile across various VHL-associated neoplasms. Compared to phase II data, kidney lesions had lower response rates, while pNET and CNS hemangioblastomas showed higher responses. These differences may reflect variations in baseline imaging timing, small patient numbers, or occasional treatment interruptions due to insurance issues or missed doses. These findings support the continued use of belzutifan in VHL disease and highlight the need for larger studies to guide long-term management of VHL-associated tumors.
利益披露 Disclosure
P. Ge, None..
M. Atta, None..
N. Srialluri, None.