Blood eosinophils as prognostic biomarkers for advanced urothelial carcinoma in patients treated with avelumab: First results of the MALVA study (Meet-URO 25).
Authors: Gambale Elisabetta , Maruzzo Marco , Messina Carlo , De Gennaro Aquino Irene , Vascotto Ismaela Anna , Rossi Virginia , Bimbatti Davide , Cavasin Nicolò , Messina Marco , Mennitto Alessia , Rebuzzi Sara Elena , Mercinelli Chiara , Fanelli Martina , Sorarù Mariella , Scolari Federico , Mela Marinella Micol , Doni Laura , Pillozzi Serena , Antonuzzo Lorenzo 
Published: June 2023

e16570 Background: Platinum-based chemotherapies (CTs) represent the standard first-line treatment of advanced urothelial carcinoma (aUC). However, the development of resistance and toxicities to these regimens is responsible for poor progression-free survival (PFS) and overall survival (OS). Maintenance treatment with the programmed death-ligand 1 (PD-L1) inhibitor avelumab after initial response to CT improved significantly OS. Despite the survival advantage, only a limited percentage of patients (pts) benefits from immunotherapy. Therefore, prognostic/predictive factors for immunotherapy are needed. Studies carried out on small cohorts of pts with melanoma, renal cell cancer or lung carcinoma proved that eosinophil count or variations could be used as prognostic factors during immunotherapy. Thus, the aim of the present study is to evaluate eosinophil levels as potential biomarker for outcome among aUC pts enrolled in the MALVA (Maintenance with AVeLumAb in advanced urothelial neoplasms in response to first-line CT: an observational retrospective and prospective study) ongoing study (Meet-URO 25). Methods: The MALVA study is an ongoing real-life multicentric retro-/prospective observational study on aUC pts receiving avelumab maintenance after response to platinum-based first-line CT. The co-primary endpoints are OS and PFS. We present here data of the first 100 enrolled aUC pts who received avelumab as maintenance therapy after response to platinum-based CT between January 2021 and January 2023. Absolute Eosinophil Counts (AEC) were registered at baseline (week 0) and at time of the first tumor assessment (week 12). This study aims to evaluate whether the AEC could be a predictive biomarker of efficacy in pts with aUC treated with avelumab. Results: One-hundred pts (median age, 72 years), 71.4% of whom were men, were enrolled (data cut off, January 2, 2023). Median follow-up time was 8.5 months. Median duration of avelumab treatment was 5.9 months. Median PFS for the entire population was 8.7 months (95% CI; 5.7 months-not reached). Predefined subgroup analyses showed PFS and OS improvement (5.1 months vs NR, p = 0.0031; 12.9 months vs NR, p = 0.056 respectively) in pts with high AEC at week 0 vs low AEC pts. Additionally, a pilot analysis was conducted for 34 pts, for whom PFS and OS were stratified by AEC at first tumor assessment (week 12). PFS was longer (6.4 months vs NR, p = 0.045) for pts with high AEC vs low AEC pts. Conclusions: In order to optimize treatment efficacy in aUC, reliable biomarkers are required. In this study, we provide data from a homogeneous cohort investigating the relevance of eosinophils in aUC pts receiving avelumab, suggesting that AEC could be an easily accessible and reproducible prognostic biomarker that warrants further studies.