Association of the Lung Immune Prognostic Index with Immunotherapy Outcomes in Mismatch Repair Deficient Tumors

• Main Authors: Edouard Auclin, Perrine Vuagnat, Cristina Smolenschi, Julien Taieb, Jorge Adeva, Laetitia Nebot-Bral, Marta Garcia de Herreros, Rosario Vidal Tocino, Federico Longo-Muñoz, Yola El Dakdouki, Patricia Martín-Romano, Lydia Gaba, Tamara Saurí, Helena Oliveres, Eduardo Castañón, Rocio Garcia-Carbonero, Benjamin Besse, Christophe Massard, Laura Mezquita, Antoine Hollebecque
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: Cancers
• Subjects: LIPI; dNLR; LDH; MSI-H; dMMR; immunotherapy
• Online Access: https://www.mdpi.com/2072-6694/13/15/3776

<b>Background:</b> 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. <b>Methods:</b> 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). <b>Results:</b> 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 (<i>p</i> < 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, <i>p</i> = 0.02. Overall, the fast-progressor rate was 16.0%, and 35.7% with poor-LIPI vs. 7.5% in the good-LIPI group (<i>p</i> = 0.02). <b>Conclusions:</b> 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.