Cardiovascular Adverse Events Associated With Bispecific T-Cell Engager Therapy

Figures

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  Figure 1. Frequency and Distribution of On-Treatment Cardiovascular Events The bar graph displays the absolute number of patients (n) who experienced each distinct cardiovascular event during the period of active therapy: left ventricular (LV) dysfunction, new atrial fibrillation (AF), acute coronary syndrome (ACS), known atrial fibrillation with rapid ventricular response (AF RVR), heart failure with preserved ejection fraction (HFpEF), supraventricular tachycardia (SVT), cerebrovascular accident (CVA) or transient ischemic attack (TIA), ventricular arrhythmias (VAs), and high-degree atrioventricular block (AVB). The numerical value positioned above each bar represents the raw percentage (proportions) of the total patient cohort that experienced that specific event. Patients could contribute to more than 1 event category if multiple distinct cardiovascular event types occurred.

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  Figure 2. Cumulative Incidence of CV Events and All-Cause Mortality Cumulative incidence function (CIF) curves for time to first cardiovascular event occurring during active therapy. Cardiovascular (CV) events and all-cause death were treated as competing risks for one another, and therapy completion without an event was treated as a competing event for both outcomes. (A) Displays the cumulative incidence for the composite CV event outcome and for all-cause mortality. (B) Displays CIF curves for grouped CV event categories. For the clarity of this figure, AF (including known AF with RVR) and SVT were grouped as atrial arrhythmias, LV dysfunction and HFpEF were grouped as heart failure, and ACS and CVA/TIA were combined into a single category. Abbreviations as in Figure 1.

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  Figure 3. Factors Associated With CVEs and the Associations Between Incident Cardiovascular Event and Mortality During T-Cell Engager Therapy Forest plots summarizing multivariable Cox models incorporating time-dependent covariates. (A) Displays adjusted HRs for covariates included in the final multivariable cause-specific model for composite cardiovascular events (CVEs), with grade ≥2 cytokine-release syndrome (CRS) and/or immune effector cell–associated neurotoxicity syndrome (ICANS) modeled as a time-dependent covariate. (B) Displays adjusted HRs for variables independently associated with on-treatment all-cause mortality, using a Cox model with the main covariate of interest, occurrence of a composite CVE, modeled as a time-dependent covariate. HRs and 95% CIs are presented on a logarithmic scale. eGFR = estimated glomerular filtration rate.

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  Figure 4. Cardiovascular, Noncardiovascular, and All-Cause Mortality During T-Cell Engager Therapy The cumulative incidence functions for cardiovascular (CV) mortality (red) and noncardiovascular mortality (blue) were estimated using a competing-risks framework. For each curve, the competing events included the alternate cause of death and completion of active therapy without death. The all-cause mortality curve (green) represents 1 minus the Kaplan-Meier survival estimate and reflects the unadjusted probability of death from any cause during active therapy.

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  Central Illustration. Cardiovascular Adverse Events Among Patients With Cancer Treated With T-Cell Engager Therapy In a dual-center cohort of 567 patients receiving T-cell engager (TCE) therapy, 60 patients experienced ≥1 on-treatment cardiovascular event (CVE) and 507 patients did not experience a CVE. The cumulative incidence of on-treatment CVEs was 10.4% (95% CI: 8.1%-13.1%), most commonly left ventricular (LV) dysfunction, and atrial fibrillation (AF). Coronary artery disease was the only baseline variable independently associated with CVEs, and development of grade ≥2 cytokine-release syndrome (CRS) and/or immune effector cell–associated neurotoxicity syndrome (ICANS) was associated with a significantly increased risk of CVEs (lower panel left). Incident CVEs were, in turn, significantly associated with all-cause mortality. Among TCE agents, teclistamab, epcoritamab, and prior anthracycline exposure were independently associated with higher on-treatment mortality. eGFR = estimated glomerular filtration rate.