抗生素使用、血浆瓜氨酸浓度与血液菌群影响PD-1单抗在NSCLC患者的疗效
创作:aluba 审核:aluba 2019年07月29日
  • 纳入72名接受纳武单抗治疗的非小细胞肺癌患者;
  • 相比于治疗开始前后使用过抗生素(EUA)的患者,未使用过抗生素的患者的总生存率显著升高(13.4 vs. 5.1个月);
  • 血浆中更高的基础瓜氨酸浓度与肿瘤应答及临床受益相关,相比于血浆瓜氨酸浓度较低的患者,血浆瓜氨酸浓度较高的患者的无进展生存期显著升高(7.9 vs. 1.6个月);
  • EUA患者的血浆基础瓜氨酸浓度更低;
  • 血液中特定细菌DNA的存在分别与肿瘤应答、临床受益及肿瘤进展相关。
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aluba
Journal for ImmunoTherapy of Cancer上发表的一项最新研究,发现在使用PD-1单抗(纳武单抗)治疗非小细胞肺癌的患者中,治疗开始前后的抗生素使用、血浆基础瓜氨酸浓度及血液菌群显著影响了治疗效果。
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Role of antibiotic use, plasma citrulline and blood microbiome in advanced non-small cell lung cancer patients treated with nivolumab

抗生素使用、血浆瓜氨酸浓度与血液菌群在接受纳武单抗治疗的晚期非小细胞肺癌患者中的作用

10.1186/s40425-019-0658-1

2019-07-10, Article

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BACKGROUND: Recent data suggested a role of gut microbiota and antibiotic use on immune checkpoint inhibitors efficacy. We aimed to evaluate the impact of early use of antibiotic (EUA), blood microbiome and plasmatic citrulline (marker of the intestinal barrier) on nivolumab efficacy in non-small cell lung cancer (NSCLC).
METHODS: We included all consecutive patients with advanced NSCLC treated with nivolumab in our Department between 2014 and 2017. Blood microbiome was analyzed at month (M) M0 and M2. Citrulline rates were evaluated at M0, M2, M4 and M6.
RESULTS: Seventy-two patients were included (EUA in 42%). Overall survival (OS) was longer without EUA (median 13.4 months) than with EUA (5.1 months, p = 0.03). Thirty-five patients (49%) had plasma samples available. High citrulline rate (≥20 μM) at M0 was associated with tumor response (p = 0.084) and clinical benefit (nivolumab > 6 months) (p = 0.002). Median progression-free survival (PFS) was 7.9 months (high citrulline) vs 1.6 months (low citrulline) (p < 0.0001), and median OS were respectively non reached vs 2.2 months (p < 0.0001). Patients with EUA had lower median citrulline rates at M0: 21 μM (IQR 15.0-30.8) vs 32 μM (IQR 24.0-42.0) without EUA (p = 0.044). The presence of specific bacterial DNA in blood at M0 was associated with response and clinical benefit (Peptostreptococcae, Paludibaculum, Lewinella) or with tumor progression (Gemmatimonadaceae). Multivariate analyses on PFS and OS confirmed the prognostic role of citrulline and blood microbiome.
CONCLUSIONS: EUA is associated with shorter OS with nivolumab and lower citrulline rates. Plasma citrulline and blood microbiome appear to be promising predictive factors of nivolumab efficacy.

First Authors:
Julia Ouaknine Krief

Correspondence Authors:
Etienne Giroux Leprieur

All Authors:
Julia Ouaknine Krief,Pierre Helly de Tauriers,Coraline Dumenil,Nathalie Neveux,Jennifer Dumoulin,Violaine Giraud,Sylvie Labrune,Julie Tisserand,Catherine Julie,Jean Francois Emile,Thierry Chinet,Etienne Giroux Leprieur

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