Risk factors indicating immune-related adverse events with combination chemotherapy with immune checkpoint inhibitors and platinum agents in patients with non-small cell lung cancer: a multicenter retrospective study

Fujimoto, Airi; Koutake, Yoshimichi; Hisamatsu, Daisuke; Ookubo, Noriko; Yabuuchi, Yurika; Kamimura, Go; Kai, Tatsuo; Kozono, Aki; Ootsu, Takahiro; Suzuki, Hiroto; Matsuo, Keisuke; Kuwahara, Kimiko; Oiwane, Yoshita; Nagata, Yuko; Tanimoto, Kenya; Sato, Eri; Suenaga, Mei; Uehara, Tomohiro; Ikari, Akira; Endo, Satoshi; Hiraki, Yoichi; Kawamata, Yosei

doi:10.1007/s00262-023-03408-4

Cited by 4 publications

(1 citation statement)

References 44 publications

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“…suggested squamous cell carcinoma, anti‐PD‐1 plus anti‐CTLA‐4 regimens, and NLR <3 as potential predictive factors for irAEs during chemoimmunotherapy induction with platinum agents in patients with NSCLC. 20 Nevertheless, further clinical evidence is warranted. Thus, this study aimed to evaluate predictive factors for irAE development and prognostic factors associated with chemoimmunotherapy in NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the association between predictive factors and the development of immune‐related adverse events and prognostic factors for chemoimmunotherapy in patients with non‐small cell lung cancer: A multicenter retrospective study

Ozawa,

Sonehara,

Hachiya

et al. 2024

Cancer Medicine

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IntroductionChemoimmunotherapy is widely used as the first‐line management of advanced non‐small cell lung cancer (NSCLC) in clinical settings. However, predictive factors associated with the development of immune‐related adverse events (irAEs) and prognostic factors for NSCLC patients undergoing chemoimmunotherapy remains largely unexplored. Therefore, in this study, we aimed to evaluate predictive factors for irAE development and prognostic factors associated with chemoimmunotherapy in NSCLC patients.MethodsThis study enrolled 199 patients with advanced and recurrent NSCLC who underwent chemoimmunotherapy across eight institutions in Nagano prefecture from December 2018 to January 2023. We examined predictive factors associated with irAE development and prognostic factors associated with overall survival (OS).ResultsAmong the patients, 106 experienced irAEs, while 93 patients did not. A total of 44 (22.1%) patients developed multiple irAEs. High serum albumin levels (Alb >3.5 g/dL) emerged as an independent predictive factor associated with irAE development in logistic regression analysis (odds ratio; 2.35, 95% confidence interval 1.27–4.34, p = 0.007). Furthermore, the development of multiple irAEs (p = 0.016), lower lactate dehydrogenase level (<223 U/L, p = 0.002), and decreased neutrophil‐to‐lymphocyte ratio (<3, p = 0.049) were identified as independent favorable prognostic factors associated with OS in multivariate Cox hazard analyses.ConclusionThe study results suggest that high serum Alb is a predictive factor for irAE development and that the presence of multiple irAEs is a favorable prognostic indicator for NSCLC patients undergoing chemoimmunotherapy.

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Section: Introductionmentioning

confidence: 99%

Evaluation of the association between predictive factors and the development of immune‐related adverse events and prognostic factors for chemoimmunotherapy in patients with non‐small cell lung cancer: A multicenter retrospective study

Ozawa,

Sonehara,

Hachiya

et al. 2024

Cancer Medicine

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Predictive value of near-term prediction models for severe immune-related adverse events in malignant tumor PD-1 inhibitor therapy

Du,

Zhang,

Zhao

et al. 2024

Human Vaccines & Immunotherapeutics

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Immune-related adverse events (irAEs) impact outcomes, with most research focusing on early prediction (baseline data), rather than near-term prediction (one cycle before the occurrence of irAEs and the current cycle). We aimed to explore the near-term predictive value of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), absolute eosinophil count (AEC) for severe irAEs induced by PD-1 inhibitors. Data were collected from tumor patients treated with PD-1 inhibitors. NLR, PLR, and AEC data were obtained from both the previous and the current cycles of irAEs occurrence. A predictive model was developed using elastic net logistic regression Cutoff values were determined using Youden’s Index. The predicted results were compared with actual data using Bayesian survival analysis. A total of 138 patients were included, of whom 47 experienced grade 1–2 irAEs and 18 experienced grade 3–5 irAEs. The predictive model identified optimal α and λ through 10-fold cross-validation. The Shapiro-Wilk test, Kruskal-Wallis test and logistic regression showed that only current cycle data were meaningful. The NLR was statistically significant in predicting irAEs in the previous cycle. Both NLR and AEC were significant predictors of irAEs in the current cycle. The model achieved an area under the ROC curve (AUC) of 0.783, with a sensitivity of 77.8% and a specificity of 80.8%. A probability ≥ 0.1345 predicted severe irAEs. The model comprising NLR, AEC, and sex may predict the irAEs classification in the current cycle, offering a near-term predictive advantage over baseline models and potentially extending the duration of immunotherapy for patients.

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Neutrophil to Lymphocyte ratio as a predictor for immune-related adverse events in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Zhang

Tan

et al. 2023

Front. Immunol.

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BackgroundThe use of immune checkpoint inhibitors (ICIs) in cancer treatment has led to an increase in immune-related adverse events (irAEs), which can cause treatment discontinuation and even fatal reactions. The purpose of this study was to evaluate the usefulness of the peripheral biomarker neutrophil to lymphocyte ratio (NLR) in predicting irAEs.MethodsA systematic search of databases was conducted to identify studies on the predictive value of NLR for irAEs. The standardized mean difference (SMD) was used to compare continuous NLR, while crude odds ratios (ORs) were calculated for categorized NLR if adjusted ORs and 95% confidence intervals (CIs) were not provided in the original study.ResultsThe meta-analysis included 47 studies with a total of 11,491 cancer patients treated with ICIs. The baseline continuous NLR was significantly lower in patients with irAEs compared to those without (SMD=-1.55, 95%CI=-2.64 to -0.46, P=0.006). Similarly, categorized NLR showed that lower baseline NLR was associated with increased irAEs (OR=0.55, 95%CI=0.41-0.73, P<0.001). Subgroup analysis revealed that the OR for predicting irAEs with NLR cut-off values of 3 and 5 was 0.4 and 0.59, respectively. Interestingly, increased baseline NLR was associated with a higher incidence of immune-related liver injury (OR=2.44, 95%CI=1.23-4.84, I2 = 0%, P=0.010).ConclusionOur study suggests that lower baseline NLR is associated with a higher risk of overall irAEs. However, further studies are needed to determine the best cut-off value and explore the efficacy of NLR in predicting specific types of irAEs.

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Risk factors indicating immune-related adverse events with combination chemotherapy with immune checkpoint inhibitors and platinum agents in patients with non-small cell lung cancer: a multicenter retrospective study

Cited by 4 publications

References 44 publications

Evaluation of the association between predictive factors and the development of immune‐related adverse events and prognostic factors for chemoimmunotherapy in patients with non‐small cell lung cancer: A multicenter retrospective study

Evaluation of the association between predictive factors and the development of immune‐related adverse events and prognostic factors for chemoimmunotherapy in patients with non‐small cell lung cancer: A multicenter retrospective study

Predictive value of near-term prediction models for severe immune-related adverse events in malignant tumor PD-1 inhibitor therapy

Neutrophil to Lymphocyte ratio as a predictor for immune-related adverse events in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

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