Tang Li-Bo, Peng Ying-Long, Yang Xiao-Rong, Li Jia-Ting, Lu Chang, Zheng Mei-Mei, Sun Lu, Yang Zheng, Yan Li-Xu, Deng Yu, Chen Zhi-Hong, Lv Si-Di, Zhou Qing, Xu Chong-Rui
School of Medicine, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou, China.
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Transl Lung Cancer Res. 2025 Feb 28;14(2):631-638. doi: 10.21037/tlcr-24-963. Epub 2025 Feb 27.
Targeted therapy has dramatically altered the treatment paradigm for some patients with inflammatory myofibroblastic tumor (IMT) that possesses specific molecular aberrations. IMT is an exceedingly rare type of sarcoma, with about 50% of cases featuring anaplastic lymphoma kinase () gene rearrangements. The treatment of IMT with ALK fusions using ALK tyrosine kinase inhibitors (TKIs) has become increasingly common. However, until now, there is a lack of evidence supporting the efficacy of third-generation ALK-TKIs in this disease category.
Here, we report the first case of a patient with advanced IMT harboring the EML4-ALK fusion gene along with two rare ALK fusion genes: PLB1-ALK, which has only been reported in two cases of lung adenocarcinoma and large cell neuroendocrine carcinoma, and unreported ALMS1-ALK. The patient achieved partial response (PR) following first-line treatment with lorlatinib and subsequently underwent successful surgical intervention.
This is the inaugural case of a third-generation ALK-TKI achieving therapeutic success in advanced IMT with complex ALK rearrangements, including rare and previously uncharacterized fusion subtypes. Although the biological functions of these two rare ALK fusions still need to be confirmed, this case underscores the dependency of ALK-rearranged IMT on ALK-mediated signaling, suggesting that third-generation ALK-TKIs may offer an optimal targeted therapeutic strategy for ALK-dependent mesenchymal tumor subtypes.
靶向治疗显著改变了某些具有特定分子异常的炎性肌纤维母细胞瘤（IMT）患者的治疗模式。IMT是一种极其罕见的肉瘤类型，约50%的病例具有间变性淋巴瘤激酶（ALK）基因重排。使用ALK酪氨酸激酶抑制剂（TKIs）治疗ALK融合的IMT已越来越普遍。然而，迄今为止，缺乏证据支持第三代ALK-TKIs在这类疾病中的疗效。
在此，我们报告首例晚期IMT患者，其携带EML4-ALK融合基因以及两种罕见的ALK融合基因：PLB1-ALK，仅在两例肺腺癌和大细胞神经内分泌癌中报道过，以及未报道过的ALMS1-ALK。该患者在接受洛拉替尼一线治疗后获得部分缓解（PR），随后接受了成功的手术干预。
这是首例第三代ALK-TKI在具有复杂ALK重排（包括罕见和以前未鉴定的融合亚型）的晚期IMT中取得治疗成功的病例。尽管这两种罕见ALK融合的生物学功能仍需确认，但该病例强调了ALK重排的IMT对ALK介导信号传导的依赖性，表明第三代ALK-TKIs可能为ALK依赖性间充质肿瘤亚型提供最佳的靶向治疗策略。
