Abstract PS5-26: Pd-l1 mRNA expression in plasma-derived exosomes predicts prognosis and response to anti-pd-l1 antibodies in unresectable locally advanced triple negative breast cancer (TNBC) treated with atezolizumab-paclitaxel
Authors: Lucrezia Raimondi, Laura Di Benedetto, Victoria Bitca, Gian Paolo Spinelli
Journal: Cancer Research (2021)

Abstract Background Despite modern therapies have improved outcomes of patients with non-TNBC cancers, patients diagnosed with unresectable locally advanced TNBC usually have poor outcome for its aggressive clinical behaviour. Over time for cancer management, predicting and monitoring response to treatments is crucial, better if through easy non-invasive procedures. Atezolizumab plus nanoparticle albumin-bound (nab)-Paclitaxel prolonged progression-free survival (PFS) and overall survival (OS) among patients with TNBC, as demonstrated by phase III IMpassion130 trial. Despite this, there is a dire need for biomarkers reflecting treatment response. In our study, we correlated plasma PD-L1 mRNA levels with prognosis and response to anti -PD-L1 antibodies in unresectable locally advanced TNBC in the era of Atezolizumab. Methods We assessed 30 consecutive patients with unresectable locally advanced TNBC treated with Atezolizumab plus nab-Paclitaxel. Blood samples were collected at time point 0 (at baseline) and after 2 months and we assessed the association between PD-L1 mRNA copies per ml in plasma-derived exosomes and response to treatment. Exosomal PD-L1 mRNA in plasma was determined using Bio-Rad QX100 digital droplet PCR system and exoRNeasy kit. Objective responses were defined following the RECIST criteria v.1.1 Results At baseline, patients with complete and partial response (CR+PR, n=11) displayed a significantly higher number of PD-L1 mRNA copies per ml compared to ones with stable or progressive disease (SD+PD, n=19) (mean value: 745.6±131.1 vs 124.7±34.4, p&amp;lt;0.001). In patients with CR and PR mean PD-L1 copies/ml were 745.6±131.1 and 175.4 at baseline vs 2 months, respectively (p=0.001).In patients with stable disease the mean ± s.e.m. values were 270±71.1 vs 217.5±17.3 copies per ml (p=0.614) while in progressive disease PD-L1 mRNA levels were 112.1±31.2 vs 454.3±46.2 copies per ml at baseline vs 2 months, respectively (p&amp;lt;0.001).Two months after the start of Atezolizumab plus nab-Paclitaxel decrease of PD-L1 mRNA copies per ml relative to pre-treatment PD-L1 mRNA copies per ml, was positively correlated with an objective response to treatment.Increase of PD-L1 mRNA copies per ml was significantly associated with worse and shorter OS: median OS in patients with increase of PD-L1 mRNA copies/ml was 5 months (range 2-7 months, 95%CI 1.1-6.1); on the other side median OS in patients with decrease of PD-L1 mRNA copies/ml was more than double (range 8-15 months) (p&amp;lt;0.001).Moreover, prolonged survival outcomes (p&amp;lt;0.001) were recorded in cases with low baseline circulating Lox1+ Myeloid-derived suppressor cells (MDSC) (r=0.62, p&amp;lt;0.001) and high Natural Killer cells (NK) (r=0.66, p&amp;lt;0.001): the NK-to-MDSC ratio (NMr) was significantly higher in patients with higher number of PD-L1 mRNA copies per ml at baseline (p=0.002). During PD-L1 blockade, 2 months after starting treatment, NK progressively raised in clinical benefit group while declined in non-responders (p=0.001) Conclusions Despite the study’s limitations, our data suggest exosomal PD-L1 is significantly associated with outcome and response to treatment. Citation Format: Lucrezia Raimondi, Laura Di Benedetto, Victoria Bitca, Gian Paolo Spinelli. Pd-l1 mRNA expression in plasma-derived exosomes predicts prognosis and response to anti-pd-l1 antibodies in unresectable locally advanced triple negative breast cancer (TNBC) treated with atezolizumab-paclitaxel [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-26.