Association Of The Lung Immune Prognostic Index With Immunotherapy Outcomes In Mismatch Repair Deficient Tumors
CANCERS(2021)
摘要
Simple Summary Deficient Mismatch Repair (dMMR) is an oncogenic path accounting for around 15% of cancers. It is considered as the first predictive marker of efficacy for immune checkpoint inhibitors (ICI). However, around 39% of cases are refractory and additional biomarkers are needed. The Lung Immune Prognostic Index (LIPI) is a score reflecting the host inflammation, based on lactate deshydrogenase level, and derived neutrophils to leucocytes ratio. We aimed to assess the LIPI as a prognostic factor for ICI efficacy in patients with dMMR tumors. We found that patients with a Poor LIPI were more likely to experience disease progression, fast progression (death within the first 3 months of ICI), and have shorter overall and progression free survivals. This score is a low-cost, simple, and accessible prognostic tool in dMMR that merits further investigation in prospective studies. Background: MSI-H/dMMR is considered the first predictive marker of efficacy for immune checkpoint inhibitors (ICIs). However, around 39% of cases are refractory and additional biomarkers are needed. We explored the prognostic value of pretreatment LIPI in MSI-H/dMMR patients treated with ICIs, including identification of fast-progressors. Methods: A multicenter retrospective study of patients with metastatic MSI-H/dMMR tumors treated with ICIs between April 2014 and May 2019 was performed. LIPI was calculated based on dNLR > 3 and LDH > upper limit of normal. LIPI groups were good (zero factors), intermediate (one factor) and poor (two factors). The primary endpoint was overall survival (OS), including the fast-progressor rate (OS < 3 months). Results: A total of 151 patients were analyzed, mainly female (59%), with median age 64 years, performance status (PS) 0 (42%), and sporadic dMMR status (68%). ICIs were administered as first or second-line for 59%. The most frequent tumor types were gastrointestinal (66%) and gynecologic (22%). LIPI groups were good (47%), intermediate (43%), and poor (10%). The median follow-up was 32 months. One-year OS rates were 81.0%, 67.1%, and 21.4% for good, intermediate, and poor-risk groups (p < 0.0001). After adjustment for tumor site, metastatic sites and PS, LIPI remained independently associated with OS (HR, poor-LIPI: 3.50, 95%CI: 1.46-8.40, p = 0.02. Overall, the fast-progressor rate was 16.0%, and 35.7% with poor-LIPI vs. 7.5% in the good-LIPI group (p = 0.02). Conclusions: LIPI identifies dMMR patients who do not benefit from ICI treatment, particularly fast-progressors. LIPI should be included as a stratification factor for future trials.
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关键词
LIPI, dNLR, LDH, MSI-H, dMMR, immunotherapy, immune checkpoint inhibitors
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