Sarcopenia and high NLR are associated with the development of hyperprogressive disease after second-line pembrolizumab in patients with non-small-cell lung cancer

The aim of this multi-center retrospective study was to evaluate the incidence of hyperprogressive disease (HPD) after second-line treatment with pembrolizumab in patients (n = 167) with metastatic non-small-cell lung cancer (NSCLC) whose tumors expressed programmed cell death ligand 1 (PD-L1) in >= 1% and to search for hematological and imaging biomarkers associated with its development. Prior to chemotherapy, neutrophil : lymphocyte ratio (NLR1) and platelet : lymphocyte ratio (PLR1), and prior to immunotherapy, NLR2 and PLR2 were retrospectively analyzed. The psoas major muscle area (PMMA) was calculated at the L3 position on computed tomography before chemotherapy (PMMA1) and before immunotherapy (PMMA2) (n = 112). Patients with increment PMMA (1-PMMA2/PMMA1) x 100 >= 10% were considered to have sarcopenia (low muscle mass). After treatment with pembrolizumab on the first computerized tomography (CT) scan evaluation, patients were subdivided as follows as: hyperprogressors (HPs), progressors (Ps), non-progressors (NPs) and pseudoprogressors (PPs). HPs had significantly higher increment PMMA levels, NLR2 and PLR2 than the other patients. Moreover, in multinomial logistic regression analysis, higher levels of increment PMMA were associated with a decreased likelihood of being a P [odds ratio (OR) = 0 center dot 81; 95% confidence interval (CI) = 0 center dot 65-0 center dot 99;P = 0 center dot 047] or an NP (OR = 0 center dot 76; 95% CI = 0 center dot 62-0 center dot 94;P = 0 center dot 012)versusan HP. Higher NLRs tended to decrease the likelihood of being a Pversusan HP (OR = 0 center dot 66; 95% CI = 0 center dot 42-1 center dot 06;P = 0 center dot 09) and significantly decreased the likelihood of being an NPversusan HP (OR = 0 center dot 44; 95% CI = 0 center dot 28-0 center dot 69;P < 0 center dot 0001). Our data suggest that a high pre-immunotherapy NLR2 and the presence of sarcopenia are potential risk factors for the development of HPD.