Abstract B022: Metabolic and immunologic effects of the fasting mimicking diet in cancer patients
Authors: de Braud Filippo , Vernieri Claudio , Huber Veronica , Cova Agata , Squarcina Paola , Milano Monica , Fucà Giovanni , Longo Valter , Rivoltini Licia 
Published: August 2018

Background: The fasting mimicking diet (FMD), a plant-based, low-calorie, low-protein, low-carbohydrate diet, modulates systemic metabolism and anticancer immunity, and displays anticancer activity in many preclinical tumor models. However, safety, metabolic, and activity data in the clinical setting are lacking. Methods: At Fondazione IRCCS Istituto Nazionale dei Tumori, a prospective study is ongoing to assess feasibility, tolerability, and metabolic effects of the FMD in cancer patients (pts) following a 5-day FMD (700 Kcal on day 1 and 300 kCal on days 2-5) every 21-28 days. This study is enrolling pts with any cancer type (except for small cell lung cancer), stage, and concomitantly administered anticancer treatment. Main exclusion criteria are: insulin-dependent diabetes, severe comorbidities, BMI &lt;20 kg/m2, recent unintentional weight loss &gt;5%. We are regularly collecting blood and urine samples before FMD initiation and at diet completion to measure diet-induced changes of metabolites and growth factors. Here we report data on metabolic modifications detected in 38 pts after the first FMD cycle, and preliminary peripheral blood immunomonitoring in selected cases. Results: 38 pts were enrolled from January 2017 to July 2017. 29 had advanced disease, and 34 were receiving concomitant anticancer therapy at study enrollment. The most represented tumor types were breast (14), prostate (4), pancreatic (4), and lung (5) cancer. All pts completed at least one cycle of FMD, and no G3-G4 adverse event (AE) were reported. After the first FMD cycle, median glycemia was reduced by 15% (p&lt;0.001), plasma IGF-1 levels by 27% (p&lt;0.001), and insulin levels by 34% (p&lt;0.001), while median triglyceride, total cholesterol, and uric acid levels increased by 31.4% (p=0.014), 11% (p&lt;0.001), and 80% (p&lt;0.001), respectively; finally, average urine ketone body levels were raised from 0.38 mg/dl (range 0-10) to 62 mg/dl (range 20-100). In 4 pts (3 breast, 1 lung) enrolled in the study, we preliminarily evaluated by 10-color cytofluorimetry the frequency and activation state of immune cell subsets in peripheral blood mononuclear cells before (day 0) and at the end (day 5) of the first FMD cycle. Our analyses revealed a rapid and marked decrease of monocytic myeloid-derived suppressor cells (MDSC)(CD11b+CD33+LINnegCD14+HLA-DRneg), mirrored by a concomitant increase of activated T cells (CD3+CD25+PD-1dim) and cytolytic NK cells (CD3negCD16+CD56dim). Granulocytic MDSC (CD11+CD33+LNnegHLA-DRnegCD15+) were also reduced in 3 pts, while the 4th patient experienced an increase of these cells due to the administration of granulocyte colony-stimulating factor (G-CSF). Conclusions: This interim analysis suggests that our FMD scheme induces remarkable modifications in systemic metabolism and immunity in a heterogeneous population of cancer pts. These data provide initial insights into the metabolic modulation mediated by FMD in clinical setting, pointing to a potential contribution of this approach in reestablishing effective antitumor immunity in cancer patients.

Citation Format: Filippo de Braud, Claudio Vernieri, Veronica Huber, Agata Cova, Paola Squarcina, Monica Milano, Giovanni Fucà, Valter Longo, Licia Rivoltini. Metabolic and immunologic effects of the fasting mimicking diet in cancer patients [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B022.