Mushtaq Rao, Cortot Alexis B, Gautschi Oliver, Mazieres Julien, Camidge D Ross
Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Université de Lille, CHU Lille, Thoracic Oncology Department, Centre National de la Recherche Scientifique, INSERM, Institut Pasteur de Lille, UMR9020-UMR-S 1277-Canther, Lille, France.
Transl Lung Cancer Res. 2022 Dec;11(12):2412-2417. doi: 10.21037/tlcr-22-329.
Prior IMMUNOTARGET registry data had suggested that responses to immune [anti PD(L)1] monotherapy in gene-arranged non-small cell lung cancer (NSCLC) were rare or absent, depending on the specific oncogene.
IMMUNOTARGET sites reporting prior registry data or new individual cases of gene rearranged NSCLC seeming to benefit from immune monotherapy were explored in detail looking to both validate their diagnosis of a functional gene rearrangement and to look for features potentially differentiating them from other such cases associated with low response rates.
Five cases of NSCLC with a gene rearrangement with reported responses or prolonged stabilization from immune monotherapy were identified in total. All had little or no prior smoking history and had programmed death-ligand 1 (PD-L1) values ranging from zero to 100%. A confirmed rearrangement partner was reported in only 2 of the cases (CD74-ROS1 and KIF5B-RET), however in one of the other three cases [analplastic lymophoma kinase (ALK)], significant benefit from a relevant prior targeted therapy was noted, also consistent with the rearrangement status being correctly assigned.
Not all driver oncogene subtypes of NSCLC are equally responsive to immune monotherapy, however even among patients with well-validated gene rearranged NSCLC which has traditionally been considered immune hyporesponsive, objective responses can occur. Additional explorations of the features associated with and underlying the immune hypo-responsiveness of most, but not all, cases of gene-rearranged NSCLC are required.
先前的免疫靶点注册数据表明，基因重排的非小细胞肺癌（NSCLC）对免疫[抗PD（L）1]单药治疗的反应很少或不存在，这取决于特定的致癌基因。
对报告了先前注册数据或新的似乎从免疫单药治疗中获益的基因重排NSCLC个体病例的免疫靶点研究点进行了详细探索，旨在验证其功能性基因重排的诊断，并寻找可能将它们与其他反应率低的此类病例区分开来的特征。
总共鉴定出5例基因重排的NSCLC病例，这些病例报告了对免疫单药治疗的反应或病情长期稳定。所有病例既往吸烟史很少或无吸烟史，程序性死亡配体1（PD-L1）值范围为0%至100%。仅2例病例报告了确诊的重排伴侣（CD74-ROS1和KIF5B-RET），然而，在其他三例中的一例[间变性淋巴瘤激酶（ALK）]中，注意到先前相关靶向治疗带来了显著益处，这也与正确分配的重排状态一致。
并非所有NSCLC驱动致癌基因亚型对免疫单药治疗的反应都相同，然而，即使在传统上被认为免疫反应低下的经过充分验证的基因重排NSCLC患者中，也可能出现客观反应。需要对大多数（但不是全部）基因重排NSCLC病例免疫反应低下相关的特征及其潜在机制进行进一步探索。
