Abstract 5068: Clonal Hematopoiesis of indeterminate potential (CHIP) in patients with advanced solid tumors treated with immune checkpoint blockers (ICB) as monotherapy: Analysis of the PREMIS study
Authors: Rodriguez Julieta Elena , Danlos François Xavier , Larive Alicia , Marabelle Aurelien , Loriot Yohann , Robert Caroline , Albiges Laurence , Frelaut Maxime , Aldea Mihaela , Besse Benjamin , Ducreux Michel , Even Caroline , Micol Jean Baptiste , Ponce Santiago , Marzac Christophe , Chaput Nathalie , Massard Christophe , Baldini Capucine 
Published: March 2024

Introduction: Clonal Hematopoiesis of indeterminate potential (CHIP) is a clonal expansion of mutations affecting genes involved in hematologic malignancies in patients without a hematological disease per se. It has emerged as a significant risk factor for cardiovascular events via skewing innate immune cells towards a pro-inflammatory state. Recently studies have shown its potential detrimental impact on overall survival in patients treated with chemotherapy. However, its impact on patients treated with immune checkpoint blockers in monotherapy remains unclear.

Objective: Our aim is to evaluate CHIP prevalence in a prospective cohort of patients treated with ICB for advanced solid tumors and its impact on patient outcomes.

Materials and methods: We performed a Next-Generation Sequencing (NGS) panel of 74-genes dedicated to hematological alterations on DNA extracted from whole blood collected before first administration of an ICB for an advanced solid tumor, within the PREMIS trial (NCT03984318). CHIP prevalence was assessed according to a variant allele frequency (VAF) threshold ≥ 2%.

Results: We included 127 pts in the analysis; 88 pts (69%) were male with a median age of 70 years [range 37-100]. Most common tumor locations were skin (29%), genitourinary (25%) and lung (19%). ICB setting was 1°L in 40% of patients; 2°L in 43%; &gt; 3°L in 17%, and the most used ICB was Nivolumab in 39% of patients. At least 1 CHIP mutation was found in 55 pts (43%). The most frequent mutations were found in DNMT3A (40%), TET2 (18%) and PPM1D (13%). Co-mutations were found in 20% of patients. Median PFS was 7.7 months (m) for CHIPm patients compared to 5.7 m in non-CHIPm patients (p=2.2) and median OS was 16.2 m in CHIPm patients compared to 14.9 m in non-CHIPm patients (p= .5). No pts developed hematological disease during the follow up.

Conclusion: CHIP is commonly found in pts with solid tumors, with a prevalence in our cohort of 43% with no statistical significance neither in PFS nor in OS in the CHIP-mutated population.

Citation Format: Julieta Elena Rodriguez, François Xavier Danlos, Alicia Larive, Aurelien Marabelle, Yohann Loriot, Caroline Robert, Laurence Albiges, Maxime Frelaut, Mihaela Aldea, Benjamin Besse, Michel Ducreux, Caroline Even, Jean Baptiste Micol, Santiago Ponce, Christophe Marzac, Nathalie Chaput, Christophe Massard, Capucine Baldini. Clonal Hematopoiesis of indeterminate potential (CHIP) in patients with advanced solid tumors treated with immune checkpoint blockers (ICB) as monotherapy: Analysis of the PREMIS study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5068.