Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors

Serino, Mariana; Freitas, Cláudia; Martins, Marco; Ferreira, Pestana; Cardoso, Cláudia Isabel; Veiga, Francisco; Santos, Vanessa; Araújo, David; Novais-Bastos, H.; Magalhães, Adriana; Queiroga, Henrique; Fernandes, Gabriela; Hespanhol, Venceslau

doi:10.1016/j.pulmoe.2022.03.003

Cited by 3 publications

(4 citation statements)

References 30 publications

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“…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%.…”

Section: Discussionmentioning

confidence: 96%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]48,[60][61][62] 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. Other than response to ICI therapy, irAE development was not associated with treatment-related characteristics (ICI agent, ICI alone or in combination with chemotherapy, and treatment line) in our study population.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Cook,

Samuel,

Meyers

et al. 2024

JAMA Netw Open

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ImportanceImmune-related adverse events (irAEs) secondary to immune checkpoint inhibitor (ICI) therapy reportedly improve overall survival (OS) in patients with non–small cell lung cancer (NSCLC). However, studies have been small and the association between irAE severity and OS remains poorly defined.ObjectiveTo examine the association between irAEs and their severity with OS in patients with locally advanced or metastatic NSCLC receiving ICIs.Design, Setting, and ParticipantsThis retrospective observational cohort study included patients with NSCLC receiving ICIs between March 1, 2014, and November 30, 2021, with follow-up until March 31, 2023. Data analysis was completed April 26, 2023. The Alberta Immunotherapy Database, a provincial, multicenter cohort, was used to capture data from patients receiving ICIs in Alberta, Canada. Participants included 803 patients 18 years or older who received at least 1 cycle of ICI (alone or with chemotherapy), agnostic to treatment line.ExposureDeveloping an irAE mandating delay or discontinuation of ICI therapy and/or systematic corticosteroids for management of toxic effects (hereinafter referred to as clinically meaningful irAEs).Main Outcomes and MeasuresThe primary outcome was association between irAEs and OS according to Kaplan-Meier analysis. Clinically meaningful irAEs were identified. Patients with poor prognosis (survival &lt;3 months) who may have died prior to irAE development were excluded from OS analysis, mitigating immortal time bias. Adjusted Cox proportional hazards regression analyses ascertained variables associated with OS.ResultsAmong the 803 patients included in the analysis, the median age of patients with irAEs was 69.7 (IQR, 63.1-75.2) years and the median age of those without irAEs was 67.5 (IQR, 60.4-73.3) years, with comparable sex distribution (139 of 295 men [47.1%] and 156 of 295 women [52.9%] with irAEs vs 254 of 505 men [50.3%] and 251 of 505 women [49.7%] without irAEs). Mitigating immortal time bias (n = 611), irAEs were associated with OS (median OS with irAEs, 23.7 [95% CI, 19.3-29.1] months; median OS without irAEs, 9.8 [95% CI, 8.7-11.4] months; P &lt; .001). No OS difference was associated with treatment in hospital vs as outpatients for an irAE (median OS, 20.8 [95% CI, 11.7-30.6] vs 25.6 [95% CI, 20.1-29.8] months; P = .33). Developing irAEs remained associated with OS in the total cohort after Cox proportional hazards regression with known prognostic characteristics (hazard ratio, 0.53 [95% CI, 0.40-0.70]; P &lt; .001).Conclusions and RelevanceIn this cohort study of 803 patients with locally advanced or metastatic NSCLC receiving ICIs, developing a clinically meaningful irAE was associated with improved OS. This association was not compromised by hospitalization for severe toxic effects. Whether and how ICI therapy resumption after an irAE is associated with OS warrants further study.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Cook,

Samuel,

Meyers

et al. 2024

JAMA Netw Open

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Identification of risk factors for gastrointestinal immune–related adverse events associated with immune check point inhibitors

Morikawa,

Nitta,

Yasuda

et al. 2024

Expert Opinion on Drug Safety

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Immune Checkpoint Inhibitors and the Exposome: Host-Extrinsic Factors Determine Response, Survival, and Toxicity

et al. 2023

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Cancer immunotherapy, largely represented by immune checkpoint inhibitors (ICIs), has led to substantial changes in preclinical cancer research and clinical oncology practice over the past decade. However, the efficacy and toxicity profiles of ICIs remain highly variable among patients, with only a fraction achieving a significant benefit. New combination therapeutic strategies are being investigated, and the search for novel predictive biomarkers is ongoing, mainly focusing on tumor- and host-intrinsic components. Less attention has been directed to all the external, potentially modifiable factors that compose the exposome, including diet and lifestyle, infections, vaccinations, and concomitant medications, which could affect the immune system response and its activity against cancer cells. We hereby provide a review of the available clinical evidence elucidating the impact of host-extrinsic factors on ICI response and toxicity.

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Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors

Cited by 3 publications

References 30 publications

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

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

Identification of risk factors for gastrointestinal immune–related adverse events associated with immune check point inhibitors

Immune Checkpoint Inhibitors and the Exposome: Host-Extrinsic Factors Determine Response, Survival, and Toxicity

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