Prognostic Value of Biomarkers in Cancer Patients Treated With Immune Checkpoint Inhibitor Therapy

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Cancer treated with immune checkpoint inhibitors (n=550). Intervention: Elevated baseline NT-proBNP levels (continuous standardized log-transformed, quartiles, and ≥125 pg/mL cutoff) vs. Lower baseline NT-proBNP levels (<125 pg/mL or Q1-Q3). Primary outcome: Composite of acute cardiovascular hospitalization or all-cause death (Adjusted HR 1.19 (per 1-SD increase in log-transformed NT-proBNP in text; 1.29 in abstract); Q4 vs Q1-Q3 adjusted HR 1.62, 95% CI 1.06-1.33, p=<0.001).

Q: What does this research mean for the field?

Elevated baseline NT-proBNP levels are independently associated with an increased risk of acute cardiovascular hospitalization and death in cancer patients receiving immune checkpoint inhibitor therapy. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Ulrike Pailer; Andreas Spannbauer; Fardin Hamidi; Aliza Veronika Braser; Martin Hülsmann; Christian Gerges; Michael Gottsauner‐Wolf; Mariann Gyöngyösi; Markus Raderer; Martin Riesenhuber; Christian Hengstenberg; Jutta K Bergler-Klein; Thomas A. Zelniker

doi:10.1016/j.jacadv.2025.102022

July 31, 2025JACC AdvancesOpen Access

Prognostic Value of Biomarkers in Cancer Patients Treated With Immune Checkpoint Inhibitor Therapy

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Key result

Elevated baseline NT-proBNP was independently associated with an increased risk of acute cardiovascular hospitalization and death (adjusted HR 1.19 per 1-SD log-increase; 95% CI 1.06-1.33) in ICI-treated cancer patients.

Why the study?

Cancer patients treated with immune checkpoint inhibitors face an increased risk of cardiovascular disease due to shared risk factors, biological mechanisms, and cardiotoxic side effects, creating an urgent need for effective risk stratification strategies.

Does baseline elevation of NT-proBNP (and hsTnT) predict the composite risk of acute cardiovascular hospitalization or all-cause death in cancer patients treated with immune checkpoint inhibitors?

Key Points

To assess the association between baseline cardiac biomarkers and the risk of acute cardiovascular hospitalizations and death in cancer patients treated with immune checkpoint inhibitor therapy.
Analyzed electronic health record data from 550 cancer patients receiving immune checkpoint inhibitors with baseline NT-proBNP levels at Vienna General Hospital between January 2017 and July 2022.
Tracked the primary composite endpoint of acute cardiovascular hospitalization or death over a median follow-up of 67 weeks (66.9 weeks, Q1-Q3: 32.5-116.8 weeks).
Applied Cox regression models adjusted for age, sex, eGFR, diabetes, coronary artery disease, heart failure, hypertension, atrial fibrillation, C-reactive protein, and LDL cholesterol.
During follow-up, 190 patients (35%) died and 103 cardiovascular hospitalizations occurred across 76 patients (14%), yielding a composite event rate of 46.7 per 100 patient-years.
Patients with NT-proBNP ≥125 pg/mL (n=388, 71%) had higher 12-month Kaplan-Meier composite event rates than those with levels <125 pg/mL (39% vs 21%, P < 0.001).
After multivariable adjustment, higher NT-proBNP remained independently associated with increased risk of cardiovascular hospitalization and death (adjusted HR: 1.29; 95% CI: 1.06-1.33; Q4 vs Q1-Q3 adjusted HR: 1.62; 95% CI: 1.22-2.16).

Study Design

Type

Cohort (n=550)

Multicenter

No

Structured PICO

Does baseline elevation of NT-proBNP (and hsTnT) predict the composite risk of acute cardiovascular hospitalization or all-cause death in cancer patients treated with immune checkpoint inhibitors?

P

Population

550 adults with cancer receiving immune checkpoint inhibitor therapy (median age 65 years, 35% female) with available baseline NT-proBNP levels and free of acute cardiovascular events at baseline, followed for a median of 66.9 weeks.

E

Exposure

Baseline cardiac biomarker elevation: NT-proBNP modeled continuously (per 1-unit increase in standardized log-transformed biomarker), by quartiles (Q4 vs Q1-Q3), and using an a priori threshold of ≥125 pg/mL (as well as hsTnT ≥14 ng/L in a subset of 305 patients).

C

Comparator

Lower baseline cardiac biomarker levels: NT-proBNP <125 pg/mL (or Q1-Q3) and/or hsTnT <14 ng/L.

O

Outcome

Composite of all-cause death or acute cardiovascular hospitalization over a median follow-up of 66.9 weeks (12-month and 24-month Kaplan-Meier event rates assessed).composite

Main Result

Hazard Ratio: 1.19 (95% CI 1.06–1.33)

Absolute Event Rate: 39% vs 21%

p-value: p=<0.001

Baseline NT-proBNP and hsTnT levels independently stratify the risk of acute cardiovascular hospitalization and mortality in cancer patients initiating immune checkpoint inhibitor therapy, supporting routine pre-treatment biomarker screening.

Limitations

Retrospective analysis with potential residual confounding
Single-center design at a tertiary academic center
Non-standardized biomarker measurement leading to incomplete data and potential selection bias
Included only in-hospital NT-proBNP measurements, excluding ambulatory or external laboratory values
Underpowered to detect differences between ICI monotherapy and combination therapy
Lack of formal adjudication for causes of hospitalization and death
Retrospective analysis with potential for residual confounding
Single-center study at a tertiary academic center
Biomarkers were not measured in a standardized manner, resulting in incomplete data and potential selection bias
Only in-hospital NT-proBNP measurements were included, excluding ambulatory or external laboratories
Not powered to detect differences between ICI monotherapy and dual ICI combination therapy
Causes of hospitalizations and deaths were not formally adjudicated

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Answers are grounded in this paper and cite their sources.

Implication

NT-proBNP elevation may aid risk stratification in ICI-treated patients; extends observational data but leaves open whether screening improves outcomes.

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved outcomes for several malignancies, but cancer patients face an increased risk of cardiovascular disease due to shared risk factors, similar biological mechanisms, and cardiotoxic side effects of therapy. Effective risk stratification strategies are urgently needed. OBJECTIVES: This study explored the association between the biomarkers with the risks of acute cardiovascular hospitalizations and death in cancer patients receiving ICI therapy. METHODS: We used electronic health records of patients treated with ICI who had available baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at Vienna General Hospital between January 2017 and July 2022. The primary outcome of interest was the composite of acute cardiovascular hospitalization heart failure or death. Cox regression models were adjusted for age, sex, estimated glomerular filtration rate, diabetes, coronary artery disease, heart failure, hypertension, atrial fibrillation, C-reactive protein, and low-density lipoprotein cholesterol. RESULTS: Among 550 patients (35% female, age 65 years), median NT-proBNP levels were 272 pg/mL (Q1-Q3: 102-742), with 388 patients (71%) having levels ≥125 pg/mL. Over a median follow-up of 67 weeks, 190 patients (35%) died, and 103 cardiovascular hospitalizations (most commonly due to stroke, coronary artery disease, and heart failure) occurred in 76 patients (14%), resulting in a primary composite endpoint rate of 46.7 events per 100 patient-years. After multivariable adjustment, NT-proBNP remained independently associated with an increased risk of cardiovascular hospitalization and death (adjusted HR for 1-SD increase in log-transformed biomarker: 1.29; 95% CI: 1.06-1.33). CONCLUSIONS: These data highlight NT-proBNP levels as a valuable marker for identifying cancer patients at increased risk for cardiovascular events during ICI therapy.

Discussion

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Cite This Study

Pailer et al. (2025) conducted a cohort in Cancer treated with immune checkpoint inhibitors (n=550). Elevated baseline NT-proBNP levels (continuous standardized log-transformed, quartiles, and ≥125 pg/mL cutoff) vs. Lower baseline NT-proBNP levels (<125 pg/mL or Q1-Q3) was evaluated on Composite of acute cardiovascular hospitalization or all-cause death (Adjusted HR 1.19 (per 1-SD increase in log-transformed NT-proBNP in text; 1.29 in abstract); Q4 vs Q1-Q3 adjusted HR 1.62, 95% CI 1.06-1.33, p=<0.001). Elevated baseline NT-proBNP was independently associated with an increased risk of acute cardiovascular hospitalization and death (adjusted HR 1.19 per 1-SD log-increase; 95% CI 1.06-1.33) in ICI-treated cancer patients.

synapsesocial.com/papers/6ae959437b4c8be1870a8b1c https://doi.org/10.1016/j.jacadv.2025.102022

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Prognostic Value of Biomarkers in Cancer Patients Treated With Immune Checkpoint Inhibitor Therapy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Prognostic Value of Biomarkers in Cancer Patients Treated With Immune Checkpoint Inhibitor Therapy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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