Relationship between caloric intakes and sensitivity to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) patients: The ELY-2 study

The fueling of lymphocytes is required for the anticancer activity of ICI. We reported in the ELY study (Boudou-Rouquette et al, EBioMedicine 2021) that increased energy expenditure – so called hypermetabolism (HM) – is associated with decreased tumor response, reduced 6-month progression-free survival (PFS) and reduced overall survival (OS) in metastatic NCSLC patients treated with ICI. Here, we investigate whether meeting caloric requirements improves the sensitivity to ICI. We retrospectively analyzed the database of the CERTIM cohort (Immuno-modulatory Therapies Multidisciplinary Study group) of patients treated with ICI for a metastatic NSCLC between 2015 and 2021. All patients had a baseline nutritional assessment including resting energy expenditure (REE) measure using indirect calorimetry, and estimation of food intake. Measured/theoretical REE ≥ 110% defined HM; otherwise, patients were classified as normometabolic (NM). Intakes ≥ 90% of measured needs defined caloric coverage. The primary endpoint was PFS. Secondary endpoints included OS. Among 162 patients, 84 (51.9%) were NM, and 78 (48.1%) HM. In HM patients, 40 (51.3%) met their caloric needs (group A) while 38 (48.7%) did not (group B). Median PFS was 4.3 vs. 1.9 months in groups A and B, respectively (HR: 0.49, 95%CI [0.31-0.80], p = 0.004). The PFS achieved in the group A and in NM patients were similar (HR: 0.99, 95%CI [0.65-1.51], p = 0.95). In multivariate analysis, caloric coverage was independently associated with improved PFS in HM patients (HR: 0.56, 95%CI [0.31 – 0.99], p = 0.048). The median OS reached 20.0 months in NM patients (HR: 0.44, 95% CI [0.30 - 0.64], p < 0.001). Among HM patients, the median OS was higher in the group A: 9.6 vs. 5.6 months (HR: 0.58, 95%CI [0.35-0.95], p = 0.03). Energy supply is a critical determinant of the sensitivity to ICI in NSCLC patients. A randomized study to evaluate the benefit of early nutritional intervention in this setting is warranted.