RANKL as Prognostic Marker in High PDL1 NSCLC

Receptor activator of nuclear factor kappa-B ligand (RANKL) can directly promote tumor growth and indirectly support tumor immune evasion by altering the tumor microenvironment (TME) and immune cell responses.

Michele Iuliani and the team aimed to assess the prognostic significance of soluble RANKL in patients with advanced non-small cell lung cancer (NSCLC) receiving programmed cell death 1 (PD1)/programmed death-ligand 1 (PDL1) checkpoint inhibitor therapy.

Researchers performed an inclusive analysis by measuring plasma RANKL levels in 100 patients with advanced NSCLC undergoing monotherapy with PD1/PDL1 checkpoint inhibitors. The optimal cut-off value was established using the Cutoff Finder package in R. Survival curves for four distinct patient groups based on their RANKL and PDL1 levels (high or low) were generated using the Kaplan-Meier method and compared with the log-rank test. The Cox regression model calculated HRs and 95% CIs for overall survival (OS) and progression-free survival (PFS).

Researchers found that the optimal RANKL cut-off was established at 280.4 pg/mL, dividing patients into high and low RANKL groups. A significant association was noted between elevated RANKL levels and decreased 24-month survival rates specifically in the high PDL1 expression subgroup (P=0.002). Furthermore, low RANKL levels combined with high PDL1 expression were associated with improved PFS (median 22 months, 95% CI 6.70 to 50 vs median 4 months, 95% CI 3.0 to 7.30, P=0.009) and OS (median 26 months, 95% CI 20 to not reached vs median 7 months, 95% CI 6 to 13, P=0.003), highlighting RANKL’s potential as an adverse prognostic indicator in these patients. Multivariate analysis confirmed RANKL as an independent negative prognostic factor for both PFS and OS, irrespective of other clinicopathological variables.

The study concluded that RANKL demonstrates significant prognostic and predictive value in patients with high PDL1 expression, emphasizing its role as a potential biomarker in advanced NSCLC treated with PD1/PDL1 checkpoint inhibitors.

The study received no funds.

Source: https://pubmed.ncbi.nlm.nih.gov/38908859/

Iuliani M, Simonetti S, Cristofani L, et al. (2024). “Circulating receptor activator of nuclear factor kappa-B ligand (RANKL) levels predict response to immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC).” J Immunother Cancer. 2024 Jun 21;12(6):e009432. doi: 10.1136/jitc-2024-009432. PMID: 38908859.