靶向DLL3的Tarlatamab治疗Selpercatinib进展后甲状腺髓样癌一例
一例RET改变型甲状腺髓样癌患者在Selpercatinib进展后接受DLL3靶向双特异性T细胞衔接器Tarlatamab治疗,采用三步递增剂量及改良的细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)监测管理方案。患者出现2级CRS和2级ICANS,无≥3级治疗相关不良事件,治疗8周后达生化与影像学完全缓解且持续中。
要点
- Selpercatinib进展后RET改变型MTC预后差,Tarlatamab为潜在选择
- 改良三步递增剂量与CRS/ICANS监测方案可能提高安全性
- 本例出现2级CRS和2级ICANS,无≥3级治疗相关不良事件
核心结论
- 改良给药与监测方案可能改善Tarlatamab在MTC患者中的安全性并保持疗效。
- 需进一步研究评估Tarlatamab在MTC中的作用。
研究设计与样本
- 单例病例报告:一例RET改变型MTC患者在Selpercatinib进展后接受Tarlatamab治疗。
- 采用三步递增剂量方案,并修改了CRS和ICANS的监测与管理流程。
主要发现
- 第1周期第1天给药后出现2级CRS和2级ICANS。
- 未发生任何≥3级治疗相关不良事件。
- 疾病相关症状快速改善。
- 治疗8周后达生化与影像学完全缓解,且缓解持续中。
临床怎么用
- 对Selpercatinib进展的RET改变型MTC,可考虑Tarlatamab并采用改良递增剂量与CRS/ICANS监测方案。
局限性
- 为单例病例报告,证据级别有限。
- 原文指出既往病例系列曾对该人群的安全性提出担忧。
- 需进一步研究评估Tarlatamab在MTC中的作用。
以上解读依据论文摘要(全文未开放获取或许可不允许翻译转载)。
原文
BACKGROUND: After progression on selpercatinib, patients with RET-altered medullary thyroid carcinoma (MTC) face a poor prognosis. Tarlatamab-a Delta-like ligand 3-targeted bispecific T-cell engager-is a promising therapeutic option for patients with MTC, but a prior case series raised safety concerns in this population. METHODS: A patient with RET-altered MTC who progressed on selpercatinib received tarlatamab using a three-step step-up dosing regimen with modified protocols for monitoring and managing cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). RESULTS: This patient experienced grade 2 CRS and grade 2 ICANS after cycle 1, day 1. He did not experience any grade ≥3 treatment-related adverse events. The patient had rapid improvement of the disease-associated symptoms. After 8 weeks of treatment, the patient experienced a biochemical and radiographic complete response that is ongoing. CONCLUSIONS: A modified dosing and monitoring protocol may improve the safety of tarlatamab in patients with MTC while maintaining efficacy. Further research is needed to evaluate the role of tarlatamab in MTC.
引用
- Roberts TJ, Meador CB, Fuld AD, et al. A Novel Approach to Targeting DLL3 with Tarlatamab in a Patient with Medullary Thyroid Carcinoma after Progression on Selpercatinib. Thyroid. 2026. PMID: 42117355. doi:10.1177/10507256261448706
供执业医师工作参考,不替代临床判断;数值与分级以指南原文为准。