Predictors of Immunotherapy Efficacy in Metastatic Non-Small Cell Lung Cancer: Lung Immune Prognostic Index and Immune-Related Toxicity

Alba Moratiel Pellitero; Maria Zapata Garcia; Marta Gascon Ruiz; Jose Miguel Arbones-Mainar; Rodrigo Lastra Del Prado; Dolores Isla

doi:10.14740/wjon1790

Predictors of Immunotherapy Efficacy in Metastatic Non-Small Cell Lung Cancer: Lung Immune Prognostic Index and Immune-Related Toxicity

World J Oncol. 2024 Apr;15(2):223-238. doi: 10.14740/wjon1790. Epub 2024 Mar 21.

Authors

Alba Moratiel Pellitero^{1

2}, Maria Zapata Garcia^{1

2}, Marta Gascon Ruiz^{1

2}, Jose Miguel Arbones-Mainar^{2

3

4}, Rodrigo Lastra Del Prado^{1

2}, Dolores Isla^{1

2}

Affiliations

¹ Medical Oncology Department, University Hospital Lozano Blesa, Zaragoza, Spain.
² Aragon Health Research Institute, Instituto de Investigacion Sanitaria Aragon (IIS Aragon), Zaragoza, Spain.
³ Instituto Aragones de Ciencias de la Salud (IACS), Zaragoza, Spain.
⁴ CIBER Fisiopatologia Obesidad y Nutricion (CIBERObn), Instituto Salud Carlos III, Madrid, Spain.

Abstract

Background: Immune checkpoint inhibitors (ICIs) have been proposed as the standard first-line and subsequent treatment for metastatic non-small cell lung cancer (NSCLC). This study analyzed whether patients with good lung immune prognostic index (LIPI) have a better response to ICIs and the relationship between immune-related adverse events (irAEs) and response in clinical practice.

Methods: This was an observational, retrospective, single-center study. Patients with stage IV NSCLC between 2016 and 2021 were included in the study. Toxicity was assessed according to The Common Terminology Criteria for Adverse Events. Response assessment was performed according to RECIST 2.0 and immuno-related criteria. Descriptive and survival analyses were conducted. Degree of toxicity and response to treatment (based on treatment and histology) were assessed. LIPI and response were assessed. LIPI included dNLR (absolute neutrophil count/(white blood cell count - absolute neutrophil count)) ≥ 3 and lactate dehydrogenase (LDH) greater than the upper limit of normal. Patients were stratified into good (G), intermediate (I), and poor (P) prognostic groups.

Results: A total of 168 patients were included (130 men and 38 women, mean age 64.3 years). ICI use in the first- or second-line treatment was 65% and 35%, respectively. Fifteen (9%) patients showed complete response (CR), 50 (30%) showed partial response (PR), 39 (22%) had stable disease (SD), 45 (28%) had progressive disease (PD), and 19 (11%) were not evaluated (NE). Patients with good prognostic LIPI (dNLR < 3 and normal LDH levels) showed a better response. Progression-free survival (PFS) was 19 months in G, 6 months in I, and 2 months in P. Overall survival (OS) was 27 months in G, 8 months in I, and 3 months in P. One hundred fourteen patients died (56% G, 76% I, 93% P). Patients with adenocarcinoma were 116 (77 with irAEs G1-4 (13 CR, 31 PR, 21 SD, eight PD, and four NE)), and without were 39 (three PR, six SD, 21 PD, and nine NE). Fifty-two patients had squamous carcinoma (27 with irAEs G1-4 (two CR, 12 PR, nine SD, and four PD)), and 25 did not (four PR, three SD, 12 PD, and six NE)). IrAEs appearance was observed in longer PFS (19 vs. 2 months) and OS (27 vs. 4 months; P < 0.0001).

Conclusions: LIPI was a positive predictor of response to ICI. The presence of irAEs is associated with a better immune response. In contrast, the absence of toxicity predicted a worse prognosis.

Keywords: Immunotherapy; LIPI; Lung cancer; Non-small cell lung cancer; Predictor; Survival; Toxicity.

Grants and funding

The project does not have financing, nor does it require resources from the institution since everything that is analyzed is part of daily practice. Researchers are not compensated financially or in any other way for their participation in the study.