Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause serious immune-related adverse events (irAEs). This study aimed to identify risk factors for all types of irAEs induced by ICIs in patients with non-small-cell lung cancer (NSCLC), by systematic review and meta-analyses. METHODS: A systematic search was performed in Pubmed, Embase and Web of Science by two independent reviewers. Studies were selected that included patients with NSCLC and evaluated characteristics of patients with and without irAEs induced by ICIs. Quality and risk of bias of the selected studies were assessed. Random effects meta-analyses were conducted to estimate pooled odds ratios (ORs) for risk factors of developing all type of irAEs, and separately for pneumonitis, interstitial lung disease and severe irAEs. With the objective of exploring sources of heterogeneity, stratified analyses were performed by quality and region. RESULTS: 25 studies met the inclusion criteria. In total, the data of 6696 patients were pooled. 33 different risk factors for irAEs were reported. irAEs of interest were reported for 1653 (25%) of the patients. Risk factors related to the development of irAEs were: C-reactive protein, neutrophil lymphocyte ratio (NLR), use of PD-1 inhibitor, high PD-L1 expression, an active or former smoking status, ground glass attenuation, and a better treatment response. CONCLUSION: The identified risk factors for the development of these irAEs are mostly related to the alteration of the immune system, proinflammatory states and loss of immunological self-tolerance. Patients identified as having a higher risk for irAEs should be monitored more closely.

Quality of life after treatment with immune checkpoint inhibitors for lung cancer; the impact of age.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment. However, it remains unclear as to whether changes in Health-Related Quality-of-Life (HRQoL) are associated with the age of lung cancer patients treated using ICIs. This study aimed to evaluate this possible association and to compare ICI-treated patients' HRQoL scores with normative data of an age-matched non-cancer general population. METHODS: Lung cancer patients from the OncoLifeS data-biobank were included if they were treated with ICIs, irrespective of other treatments, at the University Medical Center Groningen between 2015 and 2021 and had completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30), both at the start of ICI treatment and after six months. Association of age as a continuous variable (per 10 years) and changes in HRQoL scores between baseline and 6 months was assessed using multivariable regression analyses. Clinical relevance of differences in HRQoL scores between OncoLifeS and the general population was classified into trivial, small, medium, and large, for three age groups (<60, 60-69 and ≥ 70 years). RESULTS: 151 patients were included with a mean age of 65.8 years. An increase in age per 10 years was associated with a larger decrease in the summary HRQoL score(ß = -3.28,CI95%-6.42;-0.14), physical(ß = -4.8, CI95% -8.71;-0.88), cognitive(ß = -4.51,CI95%-8.24;-0.78), role functioning(ß = -5.41,CI95%-10.78;-0.05), symptom burden(ß = -3.66,CI95%-6.6;-0.73), and smaller negative changes in financial difficulties(ß = 6.5 95 % CI 3.16; 9.85). OncoLifeS HRQoL scores were lower than those of the general population and differences were most often classified as large and medium. CONCLUSION: Older lung cancer patients experience larger deteriorations in most HRQoL domains after 6 months of ICI treatment. Also, these patients showed significantly lower HRQoL scores compared to the general population.