Zoghbi Marianne, Patel Brina A, Roulleaux Dugage Matthieu, Mezquita Laura, Bahleda Rastilav, Dufresne Armelle, Brahmi Mehdi, Ray-Coquard Isabelle, Pautier Patricia, Blay Jean-Yves, Le Cesne Axel, Massard Christophe, Besse Benjamin, Auclin Edouard, Nassif Haddad Elise F
Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Département d'Innovation Thérapeutique et d'Essais Précoces, Gustave Roussy, 94805 Villejuif, France.
Cancers (Basel). 2024 Dec 3;16(23):4053. doi: 10.3390/cancers16234053.
The efficacy of immunotherapies in soft-tissue sarcomas (STSs) is limited, and biomarkers of response are lacking. The lung immune prognostic index (LIPI) is a prognostic biomarker used with immunotherapy across cancer types. This study investigates the association of LIPI with the disease control rate (DCR) and progression-free survival (PFS) in patients with STS treated with immunotherapy versus other therapies in early-phase trials.
This post hoc analysis was conducted with patients with STS from Gustave Roussy and Centre Léon Bérard between January 2012 and June 2021. The LIPI was calculated based on a derived neutrophil-to-lymphocyte ratio > 3 and elevated lactate dehydrogenase. Patients were categorized based on treatment (immunotherapy or other) and LIPI (good, intermediate, or poor). DCR was defined as the sum of stable disease and complete and partial response.
A total of 82 patients were enrolled in immunotherapy trials and 126 in the other therapy trials. In the immunotherapy group, DCR was higher in patients with good LIPI (76%; = 23/30) compared with the intermediate (50%; = 13/26) and poor LIPI groups (8%; = 1/12; < 0.001). The other-therapy group did not show significant differences in DCR by LIPI: DCR was 70% ( = 48/69), 70% ( = 21/30), and 60% ( = 6/10) in patients with good, intermediate, and poor LIPI, respectively ( = 0.86). In multivariate analyses, LIPI was independently associated with PFS in the immunotherapy group (hazard ratio = 5.97, = 0.0001) and not in the control group ( = 0.71).
LIPI is a significant independent prognostic marker for DCR in patients with STS treated with immunotherapy. In early-phase trials, LIPI could be used as a screening tool for stratification at inclusion. High neutrophil levels, which correlate with a poorer LIPI score, are likely associated with immunotherapy resistance. This relationship could explain the statistical impact of poor LIPI in the immunotherapy group.
免疫疗法在软组织肉瘤（STS）中的疗效有限，且缺乏反应生物标志物。肺免疫预后指数（LIPI）是一种用于多种癌症类型免疫治疗的预后生物标志物。本研究调查了在早期试验中接受免疫治疗与其他疗法的STS患者中，LIPI与疾病控制率（DCR）和无进展生存期（PFS）之间的关联。
对2012年1月至2021年6月期间来自古斯塔夫·鲁西研究所和里昂贝拉尔中心的STS患者进行了这项事后分析。LIPI基于推导的中性粒细胞与淋巴细胞比值>3和乳酸脱氢酶升高来计算。患者根据治疗方式（免疫治疗或其他）和LIPI（良好、中等或不良）进行分类。DCR定义为疾病稳定以及完全缓解和部分缓解的总和。
共有82例患者参加了免疫治疗试验，126例参加了其他治疗试验。在免疫治疗组中，LIPI良好的患者DCR较高（76%；23/30），而中等LIPI组（50%；13/26）和不良LIPI组（8%；1/12；P<0.001）较低。其他治疗组中，不同LIPI的患者DCR无显著差异：LIPI良好、中等和不良的患者DCR分别为70%（48/69）、70%（21/30）和60%（6/10）（P=0.86）。在多变量分析中，LIPI在免疫治疗组中与PFS独立相关（风险比=5.97，P=0.0001），而在对照组中无相关性（P=0.71）。
LIPI是接受免疫治疗的STS患者DCR的重要独立预后标志物。在早期试验中，LIPI可作为纳入时分层的筛选工具。中性粒细胞水平高与较差的LIPI评分相关，可能与免疫治疗耐药有关。这种关系可以解释不良LIPI在免疫治疗组中的统计学影响。
