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

Abstract

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 ∆PMMA (1-PMMA2/ PMMA1) × 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 ∆PMMA levels, NLR2 and PLR2 than the other patients. Moreover, in multinomial logistic regression analysis, higher levels of ∆PMMA were associated with a decreased likelihood of being a P [odds ratio (OR) = 0•81; 95% confidence interval (CI) = 0•65-0•99; P = 0•047] or an NP (OR = 0•76; 95% CI = 0•62-0•94; P = 0•012) versus an HP. Higher NLRs tended to decrease the likelihood of being a P versus an HP (OR = 0•66; 95% CI = 0•42-1•06; P = 0•09) and significantly decreased the likelihood of being an NP versus an HP (OR = 0•44; 95% CI = 0•28-0•69; P < 0•0001). Our data suggest that a high pre-immunotherapy NLR2 and the presence of sarcopenia are potential risk factors for the development of HPD.

Impact of Sarcopenia and Inflammation on Patients with Advanced Non-Small Cell Lung Cancer (NCSCL) Treated with Immune Checkpoint Inhibitors (ICIs): A Prospective Study

“…At the same time, sarcopenia seems to be characterized by a low-degree systemic inflammation with increased levels of pro-inflammatory cytokines. Together, these data are in line with the literature [ 12 , 15 , 29 , 32 , 37 ] which underlines the correlation between sarcopenia and the presence of a basal inflammatory status.…”

“…However, in the new scenario of ICI, only a few retrospective studies highlighted how basal sarcopenia is associated with worse prognosis in advanced cancer patients [ 6 , 22 , 23 , 24 , 25 , 32 , 33 , 34 ]. According to a recent systematic review and meta-analysis (nine cohort studies consisting of 740 patients with advanced cancer receiving ICI), sarcopenia resulted as an independent, unfavorable prognostic factor in these patients.…”

Association of Dynamic Changes in Peripheral Blood Indexes With Response to PD-1 Inhibitor-Based Combination Therapy and Survival Among Patients With Advanced Non-Small Cell Lung Cancer

“…In recent years, peripheral blood biomarkers representing tumor burden or inflammation have been increasingly studied for the purpose of predicting NSCLC treatment effect. The lower pre-treatment level or post-treatment declination of those biomarkers was previously shown to associate with the higher response rate and better prognosis in the patients (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). However, most studies were based on monotherapy, and the meaningfulness of baseline values remains controversial.…”

Sarcopenia’s Prognostic Impact on Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

“…We then performed full-text reviews based on the inclusion criteria. We excluded articles that defined sarcopenia as differences in SMI between pre-treatment and posttreatment [20][21][22] or those that did not show HRs of OS and/or PFS [23][24][25][26][27][28][29][30][31]. Finally, 14 studies with a total of 1284 patients were included in this study [12][13][14]19,[32][33][34][35][36][37][38][39][40][41].…”