Predictive Factors Correlated with the Development of Immune-Related Adverse Events in Patients with Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

Abstract

Similar to the neutrophil-to-lymphocyte ratio and lung immune prognostic index (LIPI), immune-related adverse events (irAEs) were favorable prognostic factors in several studies, for patients with non-small cell lung cancer who received immune checkpoint inhibitors (ICIs). However, few studies have investigated patient characteristics and markers that predict the development of irAEs, and factors predicting the development of irAEs have not been clarified. Thus, the present study aimed to examine the predictive factors correlated with the development of irAEs in non-small cell lung cancer (NSCLC) patients who received antiprogrammed cell death protein 1/programmed cell death ligand 1 inhibitor monotherapy. Patients and Methods: The present study was retrospectively enrolled 113 advanced NSCLC patients who received ICIs between February 2016 and May 2021 and was conducted at Shinshu University Hospital. All patients were divided into two groups according to with or without of irAEs. We compared the clinical findings and laboratory data between the two groups and considered predictive factors correlated with the development of irAEs. Results: Forty-four (38.9%) patients developed irAEs of any grade. The most common irAEs were hypothyroidism (12.4%), followed by skin rash (7.1%) and interstitial lung disease (7.1%). The survival time in patients with irAEs was significantly more prolonged compared to those without irAEs (median progression-free survival: 6.8 vs 2.1 months, p < 0.001; median overall survival: 25.3 vs 9.6 months, p = 0.001). Multivariate analyses based on logistic regression revealed independent predictive factors that correlated with the development of irAEs to be first-line ICI treatment and a score of 0 or 1 on LIPI. Conclusion:The present study revealed that lines of immunotherapy and LIPI were correlated with the development of irAEs in NSCLC patients who received ICIs and can help clinicians who manage patients experiencing irAEs receiving ICIs.

Immune-Related Adverse Events and Survival Among Patients With Metastatic NSCLC Treated With Immune Checkpoint Inhibitors

“…The incidence of reported irAEs in NSCLC varies widely, ranging from 24.0% to 70.5%. This reflects heterogeneity including in study setting (observational vs randomized clinical trial), patient characteristics (cancer stage, PD-L1 status, geographical location, race and ethnicity), treatment parameters (ICI agent used either alone or combined with chemotherapy, treatment line), and irAE grading . In our cohort, the incidence of clinically meaningful irAEs was 37.0%.…”

“…Why irAEs occur in some patients but not others remains poorly understood, but a variety of predictive factors in NSCLC have been described. Demographic characteristics (age, sex, race, body mass index, and ECOG), concomitant medications (corticosteroids, proton pump inhibitors, and antibiotics), peripheral laboratory markers (hemoglobin, albumin, C-reactive protein, and others), tumor characteristics (histology, stage, PD-L1 expression, driver mutation status, and disease burden), and treatment-related factors (treatment line, response, ICI agent, concurrent chemotherapy, time to starting ICI, cumulative dose, and cumulative cycles of ICI) are inconsistently reported as predictive factors associated with irAE development . In our cohort, we identified several baseline patient characteristics associated with irAE development: 60 years or older, ECOG performance status 0, high expression of PD-L1, absence of bone metastases, DNLR of 3 or less, and levels of hemoglobin, albumin, and LDH within reference range.…”

“…It is well established that although ICIs improve clinical outcomes in NSCLC, they are complicated by immune-related adverse events (irAEs), the incidence of which varies by study setting, patient selection, treatment parameters, and irAE grading . There is growing recognition across solid malignant neoplasms that irAEs affect overall survival (OS).…”

Toxic epidermal necrolysis induced by sintilimab in a patient with advanced non-small cell lung cancer and comorbid pulmonary tuberculosis: A case report

“…Several predictive risk factors were associated with ICIinduced ir-AEs in the treatment of advanced NSCLC. According to previous reports, first-line treatment with ICIs and lung immune prognostic index (LIPI) were independent predictive risk factors for ir-AEs in patients with advanced NSCLC (14). Furthermore, concomitant chemotherapy use, high body mass index (BMI), and presence of epidermal growth factor receptor (EGFR) mutation were significant predictors for ir-AEs (15).…”

Symptoms, symptom clusters and associated factors among Chinese cancer patients receiving immune checkpoint inhibitor therapy: a cross-sectional survey

“…Negative relationships between disease course and the musculoskeletal, respiratory and nonspeci c symptom clusters was found in our study, with a shorter disease course associated with a higher symptom burden. It has been reported that patients treated with rst-line ICI therapies are more likely to develop irAEs but have better clinical outcomes [24]. Patients with a short disease course are mostly treated with rst-line ICI therapies or combined therapies, which may induce a better immune response but also the development irAEs, leading to various symptoms.…”