Risk assessment and outcomes across the clinical spectrum of cardiotoxicity from immune checkpoint inhibitors

Ended Project Grant Awarded Last action

Award ID
F32HL176198
Recipient
Awarding agency
Obligated
$161,903

Award facts

Assistance listing
93.837 Cardiovascular Diseases Research
Completion date
Place of performance
Palo Alto, CA 94305, USA

Award details come from USAspending.gov.

Description

Abstract
Immune checkpoint inhibitors (icis) have revolutionized cancer therapy, providing lifesaving treatments for an increasing number of malignancies. However, icis have also been associated with off-target multi-organ immune-related adverse events, including an increasing incidence of cardiovascular toxicities. After early reports of acute fulminant ICI-myocarditis, active surveillance of ICI cardiotoxicity using cardiac biomarkers such as troponin-i has been recommended. This has resulted in the increased detection of asymptomatic, low- grade cases of unknown natural history and clinical significance. This study will address critical knowledge gaps by investigating risk stratification and outcomes across the entire spectrum of ICI cardiotoxicity subtypes. The applicant's central hypothesis is that a subset of patients with abnormal troponin-i levels who are asymptomatic have lower risks of adverse cardiac outcomes compared to those with symptomatic disease, and peripheral biomarkers like troponin-i and novel immune markers can help distinguish between "higher" and "lower" risk patients who may tolerate safe continuation of icis. To test this hypothesis, the applicant will (1) retrospectively examine cardiac and oncologic outcomes associated with ICI cardiotoxicity stratified by patient symptoms and troponin-i measurements; (2) retrospectively examine the risks of ICI continuation after asymptomatic troponin-i elevation during ICI therapy; and (3) prospectively investigate the role of cardiac, established inflammatory, and novel immune biomarkers in predicting cardiac risks after ICI continuation. These aims will leverage comprehensive data from the stanford troponin monitoring cohort, consisting of > 1591 consecutive cancer patients with prospectively collected serial troponin-i measurements during each cycle of icis, and the international ICI- myocarditis registry of > 700 patients with confirmed ICI-myocarditis. The results of this study will lead to critical advances in the field of cardio-oncology by enhancing cardiac risk assessment for icis and establishing, for the first time, the role of biomarkers in evaluating the risks of ICI continuation after troponin-i elevation. This will have serious implications for the safe continuation of potentially lifesaving cancer therapies in affected patients. Through this fellowship training, the applicant will also gain important competencies to advance in her long-term goal of becoming a leading physician-scientist in the clinical phenotyping of cardiotoxicity from cancer therapies and forging evidence- based practices in cardio-oncology.

Transactions

Action Obligated Date
Amendment $0
Amendment -$5,961
Amendment $83,932
Amendment $83,932
Original award $0

Quick answers

Who received award F32HL176198?

F32HL176198 was awarded to The Leland Stanford Junior University by National Heart Lung and Blood Institute (National Institutes of Health) on January 31, 2025.

How much is award F32HL176198 worth?

$161,903 has been obligated on F32HL176198.

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