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

Lung Cancer

Clin Exp Immunol. 2020 Aug 5. doi: 10.1111/cei.13505. Online ahead of print.


OBJECTIVES: The aim of this multicenter retrospective study was to evaluate the incidence of hyperprogressive disease (HPD) after second-line treatment with pembrolizumab in patients (n=167) with metastatic nonsmall-cell lung cancer (NSCLC) whose tumors expressed programmed death-ligand-1 in ≥1% and to search for haematological and imaging biomarkers associated with its development.

MATERIALS AND METHODS: Prior to chemotherapy neutrophil-to-lymphocyte ratio (NLR1) and platelet-to-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).

RESULTS: After treatment with pembrolizumab on the first CT scan evaluation patients were subdivided as follows as: hyperprogressors (HPs), progressors (Ps), nonprogressors (NPs), 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 (OR, 0.81; 95% CI, 0.65-0.99; p=0.047) or a NP (OR, 0.76; 95% CI, 0.62-0.94; p=0.012) vs an HP. Higher NLRs tended to decrease the likelihood of being a P vs an HP (OR, 0.66; 95% CI, 0.42-1.06; p=0.09) and significantly decreased the likelihood of being an NP vs an HP (OR, 0.44; 95% CI, 0.28-0.69; p<0.0001).

CONCLUSIONS: Our data suggest that a high preimmunotherapy NLR2 and the presence of sarcopenia are potential risk factors for the development of HPD.