Cardiovascular Adverse Events Associated With Bispecific T-Cell Engager Therapy.

T-cell engager (TCE) therapies are bispecific or multispecific antibodies that simultaneously bind a T-cell receptor complex (usually CD3) and a tumor-associated antigen on target cells, thereby redirecting cytotoxic T cells to recognize and kill tumor cells. TCEs have significantly improved the prognosis of patients with hematologic malignancies and are being explored in solid tumors, resulting in expanding clinical indications. 1 TCEs are now approved for several B-cell and plasma-cell malignancies, including blinatumomab for B-cell precursor acute lymphoblastic leukemia; teclistamab, talquetamab, and elranatamab for multiple myeloma; and glofitamab and epcoritamab for B-cell non-Hodgkin lymphomas. 1 , 2 Other agents, such as cevostamab, are under advanced clinical investigation. Compared with chimeric antigen receptor (CAR) T-cell therapy, TCEs are “off-the-shelf” biologics that can be administered immediately without patient-specific cell manufacturing, offering broader accessibility and facilitating integration into clinical practice.

However, like other immune-based therapies, TCEs have important treatment-related toxicities, including cytokine-release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), infusion-related reactions, systemic infections, cytopenias, and tumor flare reactions. 2 Although cardiovascular complications following other immunotherapies, such as immune checkpoint inhibitors or CAR T-cell therapy, are well described (reported prevalence 0.4%-2.0% 3 and 14.0%-18.0%, 4 , 5 respectively), data on cardiovascular complications associated with TCE therapy are scarce. Recently, Sayed et al 6 described bispecific TCE therapy–related cardiovascular adverse events using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). However, FAERS is limited by reporting bias and does not capture all drug-exposed individuals, precluding accurate incidence estimation or causal inference. In this retrospective study, we aimed to describe the frequency of cardiovascular complications and baseline factors associated with these events in a large cohort of patients with cancer treated with TCE therapy.

Methods

Study design

This retrospective cohort study included consecutive patients with a cancer diagnosis who received TCE therapy between January 2016 and December 2024 at 2 large cancer centers: the Massachusetts General Brigham (MGB) Health System and the Dana-Farber Cancer Institute. The study protocol was approved by the MGB Institutional Review Board, and the requirement for informed consent was waived given the retrospective nature of this study.

Study population

We queried the MGB Research Patient Data Registry to identify adult patients with cancer (≥18 years) who initiated their first course of Food and Drug Administration–approved bispecific TCE therapy (blinatumomab, teclistamab, talquetamab, elranatamab, glofitamab, epcoritamab) between January 2016 and December 2024, including both research and nonresearch use. Patients who received at least 1 full dose of TCE therapy were included. The electronic medical records of those identified were manually reviewed (O.I.B.Z., A.N.) to obtain demographic and clinical data (including TCE therapy–related complications and management), as well as laboratory and imaging data.

Definition of individual cardiovascular events

Left ventricular (LV) systolic dysfunction was defined as either: 1) a new reduction in left ventricular ejection fraction (LVEF) of ≥10 percentage points from baseline to an LVEF <50%; or 2) a new reduction in LVEF of <10 percentage points from baseline to an LVEF of 40% to 49% with either a new relative decline in LV global longitudinal strain (GLS) of >15% from baseline or a new rise in cardiac biomarkers. 7 , 8 Because LV GLS and troponin measurements at baseline and during active therapy were infrequently obtained in our cohort, LV dysfunction was effectively defined by criterion 1 (a new reduction in LVEF of ≥10 percentage points from baseline to an LVEF <50%).

Symptomatic heart failure with reduced ejection fraction (HFrEF) was defined as LV systolic dysfunction accompanied by symptoms of heart failure (dyspnea and/or orthopnea). Heart failure with preserved ejection fraction (HFpEF) was defined as at least 1 heart failure symptom (dyspnea and/or orthopnea) plus 1 or more objective signs of volume overload (chest imaging with pulmonary infiltrates and/or pulmonary edema and/or N-terminal prohormone of brain natriuretic peptide above the normal range) that responded to loop diuretics.

Atrial arrhythmia events were defined as new-onset atrial fibrillation or atrial flutter (AF) or known AF complicated by rapid ventricular response requiring intravenous rate control or pharmacologic or electrical cardioversion. Supraventricular tachycardia included atrioventricular nodal reentrant tachycardia or atrial tachycardia and was considered a cardiovascular event when associated with rapid ventricular response requiring intravenous rate control or pharmacologic or electrical cardioversion. Ventricular arrhythmias were defined as ventricular tachycardia or ventricular fibrillation. High-degree atrioventricular conduction disease was defined as second-degree Mobitz II or third-degree atrioventricular block on a 12-lead electrocardiogram.

Acute coronary syndrome was defined per the 2025 American College of Cardiology/American Heart Association (AHA) guideline for the management of patients with acute coronary syndrome. 9 Cerebrovascular accident (CVA) and transient ischemic attack (TIA) were defined per the 2021 AHA/American Stroke Association guideline for the prevention of stroke. 10

TCE therapy–related complications

CRS and ICANS were graded according to the American Society for Transplantation and Cellular Therapy consensus criteria 11 ( Supplemental Table 1 ).

Clinical covariates

Preexisting cardiovascular disease and cardiovascular risk factors were extracted by manual chart review, including hypertension, diabetes mellitus, dyslipidemia, current or former smoking (self-report), AF, prior CVA/TIA, HFrEF, light-chain (AL) amyloid cardiomyopathy, and obstructive coronary artery disease (defined as diameter stenosis of 50% or more in the left main coronary artery or stenosis of 70% or more in a major epicardial vessel). AL amyloid cardiomyopathy was defined by Congo red–positive endomyocardial biopsy or cardiac magnetic resonance imaging findings compatible with amyloid infiltration in the presence of AL amyloid deposits confirmed by a positive Congo red stain and liquid chromatography mass spectrometry typing in a different organ. Established cardiovascular disease was defined as baseline AF, coronary artery disease, CVA/TIA, and/or HFrEF.

Cardiac testing was performed at the discretion of the treating clinician and was not prespecified. Echocardiographic variables (LVEF, LV GLS, pericardial effusion [included if more than trivial]) were collected at baseline and during TCE therapy based on the formal interpretations documented in the echocardiography reports.

Inflammatory biomarkers before and during TCE therapy were drawn per institutional protocols; peak values were identified. Biomarkers included C-reactive protein (normal reference range 0-3 mg/L), interleukin-6 (normal reference range <7.1 pg/mL), and ferritin (normal reference range 30-400 μg/L).

Study outcomes

Cardiovascular events and survival were assessed during TCE therapy, defined as the interval from the first TCE dose to 90 days after the last TCE dose. Cardiovascular events were defined as a composite of new LV systolic dysfunction with or without symptomatic heart failure (HFrEF), HFpEF, acute coronary syndrome, AF, clinically significant supraventricular tachycardias, ventricular arrhythmias, high-degree atrioventricular conduction disease, and TIA/CVA. Other outcomes of interest included individual cardiovascular events, all-cause mortality, and cardiovascular mortality. Mortality status and cause of death (cardiovascular vs other) were determined from the electronic medical record or death certificates, where available.

Statistical analysis

Continuous variables were reported as median (25th-75th percentiles [Q1-Q3]) and categorical variables as frequencies and proportions. Baseline characteristics were summarized descriptively without formal hypothesis testing between groups because of informative censoring in the time-to-event framework. Paired comparisons of LVEF and GLS between baseline and during active therapy were performed using the Wilcoxon signed-rank test. Follow-up was assessed using restricted mean follow-up time because the reverse Kaplan-Meier curve did not reach 50% and median follow-up could not be estimated. For time-to-event analyses, restricted mean time to first cardiovascular event (restricted mean time to failure) was calculated as a measure of average event-free time during the active TCE treatment period with CIs estimated using nonparametric bootstrap resampling (1,000 iterations).

Cumulative incidence function (CIF) curves were generated using the Aalen-Johansen estimator to account for competing risks. Because analyses were restricted to events occurring during TCE therapy, patients who completed therapy without an event were treated as a competing risk rather than censored because they were no longer at risk once treatment ended. 12 CIFs were calculated for the composite cardiovascular events outcome and for all-cause mortality, treating each outcome as a competing event for the other. In a separate analysis, the CIF for cardiovascular mortality was estimated, treating noncardiovascular death as a competing event.

Before model construction, collinearity among candidate variables was assessed using variance inflation factors. For analysis of the composite cardiovascular endpoint, known AF with rapid ventricular response events were excluded to reduce misclassification bias. Univariable Fine-Gray models were used to evaluate associations with the composite endpoint; variables with P < 0.05 were considered for multivariable analysis, with age and sex forced into the model. Multivariable Fine-Gray models were constructed using forward stepwise selection guided by the Akaike information criterion (AIC) to minimize overfitting. Fine-Gray model results are presented as the subdistribution HR with 95% CI. Covariates retained in the stepwise procedure were subsequently incorporated as baseline covariates in cause-specific Cox proportional hazards models evaluating cardiovascular events, with CRS and/or ICANS grades ≥2 included as a time-dependent covariate.

For all-cause mortality, univariable Cox proportional hazards models were first fitted. Variables meeting the prespecified selection criteria ( P < 0.05, with age and sex forced into the model) were entered into a forward stepwise AIC-guided multivariable Cox model. The composite cardiovascular event endpoint, including known AF with rapid ventricular response, was incorporated as a time-dependent exposure to assess its association with subsequent mortality. Cox model results are presented as the HR with 95% CI. Missing data were handled using complete-case analysis, resulting in the exclusion of 4 patients with missing baseline estimated glomerular filtration rate (eGFR). A 2-sided P value of less than 0.05 was considered statistically significant. Statistical analysis was performed using RStudio, version 1.4.1106.

Results

Baseline characteristics

The study cohort included 567 patients with cancer who received their first course of TCE therapy between January 2016 and December 2024. Baseline characteristics are shown in Table 1 . Median age at the first TCE infusion was 67 years (Q1-Q3: 57-75), and 46.0% (n = 261) were female. Among these patients, 8.6% (n = 49) had a history of obstructive coronary artery disease, 15.3% (n = 87) had AF, 7.4% (n = 42) had known HFrEF or amyloid cardiomyopathy, and 3.7% (n = 21) had a history of CVA/TIA.

The most common malignancies were multiple myeloma (n = 232, 40.9%), including 13 with concomitant AL amyloidosis, and acute lymphoblastic leukemia (n = 202, 35.6%). Overall, 217 (38.3%) patients were previously treated with anthracyclines, 130 (22.9%) with carfilzomib, and 125 (22.0%) with CAR T-cell therapy.

Clinical characteristics during TCE therapy

The restricted mean follow-up was 248 days (range: 0-973) and the most frequently used TCE agents were CD19-targeting blinatumomab (n = 212, 37.4%) and B-cell maturation antigen–targeting teclistamab (n = 167, 29.5%) ( Table 2 ). CRS and ICANS occurred in 256 (45.1%) and 46 (8.1%) patients, respectively, and were most frequent during the first cycle of TCE therapy. Grade ≥2 CRS and/or ICANS occurred in 88 (15.5%) patients.

Cardiovascular outcomes during active TCE therapy

During TCE therapy, a total of 65 cardiovascular events were observed. Figure 1 summarizes the number of patients experiencing each distinct cardiovascular event category, with 4 patients experiencing more than 1 event type. The 943-day cumulative incidence of a first cardiovascular event was 10.4% (95% CI: 8.1-13.1) in the presence of competing risks ( Figure 2 ). Cardiovascular events occurred early after TCE initiation, with a restricted mean time to failure of 91.3 days (95% CI: 65.1-113.3). The most common cardiovascular events were new LV dysfunction (n = 13, cumulative incidence of 2.3%; 95% CI: 1.3-3.8; 11 of 13 were symptomatic HFrEF) and new-onset AF (n = 12, cumulative incidence 2.1%; 95% CI: 1.2-3.6). Nine patients experienced acute coronary syndrome (cumulative incidence 1.6%; 95% CI: 0.8-2.9); 6 of 9 had acute myocardial infarction.

Baseline characteristics of patients with and without a cardiovascular event are shown in Table 1 . Among patients with concomitant multiple myeloma and AL amyloidosis (n = 13), 4 cardiovascular events were documented: new AF (n = 1), clinically significant supraventricular tachycardia (n = 1), acute coronary syndrome (n = 1), and stroke (n = 1). No heart failure events were documented.

Echocardiographic findings during therapy

Baseline echocardiography was available in 491 patients (86.6%), with a median LVEF of 62% (Q1-Q3: 58-66). During TCE therapy, 291 patients (51.3%) underwent echocardiography at a median of 61 days (Q1-Q3: 0-101) after TCE initiation; median LVEF was 60% (Q1-Q3: 57-65) ( Table 2 ). Among patients with paired baseline and on-treatment echocardiograms (n = 256), LVEF did not change significantly (paired Wilcoxon signed-rank test; P = 0.50) ( Table 2 , Supplemental Figure 1 ). Similar LVEF findings were observed in patients with established cardiovascular disease at baseline (n = 84 pairs; P = 0.87) and in those without established cardiovascular disease (n = 172 pairs; P = 0.35) ( Supplemental Figure 1 ).

LV GLS was available at baseline in 135 patients and during therapy in 99 patients, with 32 paired measurements; there was no significant change from baseline to on-treatment (paired Wilcoxon signed-rank test; P = 0.99). Hemodynamically insignificant pericardial effusions were observed in 4.6% of patients (n = 12) during TCE therapy; no patients presented with acute pericarditis.

Clinical factors associated with cardiovascular events

In univariable Fine-Gray analyses, older age, reduced renal function, baseline coronary artery disease, hypertension, dyslipidemia, prior pomalidomide/thalidomide exposure, and elranatamab therapy were associated with a higher incidence of composite cardiovascular events ( Supplemental Table 2 ). Forward stepwise Fine-Gray selection using AIC, with age and sex forced into the model, identified coronary artery disease and eGFR as covariates that improved multivariable model fit. In the final model, coronary artery disease remained the only variable independently associated with cardiovascular events (subdistribution HR: 4.06; 95% CI: 2.02-8.15), whereas age, sex, and eGFR were not statistically significant ( Supplemental Table 3 ).

Among patients with preexisting coronary artery disease, treatment-associated cardiovascular events included acute coronary syndrome (n = 5), HFrEF (n = 4), atrial fibrillation (n = 6), supraventricular tachycardia (n = 2), HFpEF (n = 1), ventricular arrhythmia (n = 1), and cerebrovascular events (n = 1). The cumulative incidence of events stratified by baseline coronary artery disease is shown in Supplemental Figure 2A (Gray’s test; P < 0.001).

To evaluate the contribution of acute immunotoxicity to cardiovascular risk, grade ≥2 CRS and/or ICANS was included as a time-dependent covariate in a cause-specific Cox proportional hazards model using the same AIC-selected baseline covariates. In univariable analysis, this exposure was associated with more than a 2-fold increase in the instantaneous risk of cardiovascular events (HR: 2.37; 95% CI: 1.26-4.46). This association remained significant after adjustment for age, sex, coronary artery disease, and eGFR (HR: 2.27; 95% CI: 1.20-4.29; P = 0.012) ( Figure 3A , Supplemental Table 4 ). Coronary artery disease remained independently associated with cardiovascular risk (HR: 3.70; 95% CI: 1.94-7.06; P < 0.001), whereas age, sex, and eGFR were not significantly associated with this outcome. The cumulative incidence of cardiovascular events stratified by CRS and/or ICANS status is shown in Supplemental Figure 2B .

Cardiovascular and all-cause mortality

Among the 106 patients who died during TCE therapy, 2 died from cardiovascular causes (severe valvular disease and deterioration of preexisting cardiomyopathy), corresponding to a cumulative incidence of 0.4% (95% CI: 0.1-1.2). Figure 4 depicts on-treatment cardiovascular, noncardiovascular, and all-cause mortality.

In univariable Cox models, older age, sex, reduced renal function, a history of cardiomyopathy/HFrEF, lower baseline LVEF, prior pomalidomide/thalidomide exposure, anthracycline exposure, and cancer/TCE agent category were each associated with higher on-treatment all-cause mortality ( Supplemental Table 5 ). To identify baseline predictors of mortality at the time of TCE initiation, a multivariable Cox model was constructed using forward stepwise selection guided by the AIC, with age and sex forced into the model. In the final multivariable Cox model, teclistamab (HR: 4.10; 95% CI: 1.90-8.84), epcoritamab (HR: 3.95; 95% CI: 1.86-8.40), and prior anthracycline exposure (HR: 2.72; 95% CI: 1.42-5.23) remained independently associated with higher on-treatment mortality along with older age and sex ( Supplemental Table 6 ).

To assess whether incident cardiovascular toxicity was associated with subsequent mortality risk, a multivariable Cox model was constructed in which the composite cardiovascular event endpoint was incorporated as a time-dependent covariate. The occurrence of a cardiovascular event was associated with subsequent mortality, with event onset conferring nearly a 7-fold increase in hazard (HR: 6.76; 95% CI: 4.19-10.92), independent of age, sex, TCE agent, and prior anthracycline exposure ( Figure 3B , Supplemental Table 7 ).

Discussion

To our knowledge, this is the first study to systematically characterize TCE-related cardiovascular complications and their association with all-cause mortality in a large, real-world cohort of patients with hematologic malignancies ( Central Illustration ). In this dual-center cohort of 567 patients treated with TCEs, the cumulative incidence of on-treatment cardiovascular events was 10.4% (95% CI: 8.1-13.1), with LV dysfunction, and AF, representing the most common presentations. Coronary artery disease was the only baseline variable independently associated with cardiovascular events, whereas development of high-grade CRS and/or ICANS was associated with a significant time-dependent increase in cardiovascular risk. Cardiovascular events were, in turn, associated with subsequent all-cause mortality. In addition, prior anthracycline exposure and treatment with teclistamab or epcoritamab were independently associated with higher mortality.

Immunotherapy has transformed cancer treatment and improved survival outcomes. However, off-target immune activation has been associated with adverse cardiovascular events. Acute myocarditis, although rare (0.4%-2%), 3 is a potentially fatal complication of immune checkpoint inhibitors, with reported mortality rates ranging from 5% to 46%. 13 , 14 In contrast, CAR T-cell therapy–related cardiovascular complications occur in 14% to 16% of patients 4 , 5 and primarily include atrial arrhythmias (8%) and HFrEF (8%), 5 with substantially lower cardiovascular mortality rates (0.50%-0.65%). 4 , 5

In a pharmacovigilance analysis of 3,668 systemic adverse events linked to TCE therapy, cardiovascular events comprised a small subset and included heart failure (1.4%), tachyarrhythmias (1.2%), myocarditis (0.2%), pericarditis (0.1%), and sudden death (0.05%). 6 Collectively, data suggest that TCE therapy is associated with a more favorable cardiovascular safety profile relative to other immunotherapeutic modalities. Consistent with this, our findings demonstrate a cumulative incidence of TCE therapy–related cardiovascular events (10.4%), most commonly HFrEF and AF, with cardiovascular mortality remaining rare (0.4%). No cases of TCE-related acute myocarditis were identified on detailed manual chart review. Although our ability to detect subclinical myocardial injury was limited by inconsistent biomarker assessments, clinical suspicion for myocarditis was low. This aligns with observations from large CAR T-cell therapy studies in which CRS and ICANS are common complications and myocarditis has not been reported. 4 , 5

Another notable finding in this cohort was the relatively low cumulative incidence of high-grade CRS or ICANS (16%), a pattern that may reflect contemporary practice characterized by heightened clinical vigilance and early use of targeted anticytokine therapies such as tocilizumab and anakinra. 11 Nevertheless, among patients receiving TCE therapy, development of grade ≥2 CRS and/or ICANS was associated with more than a 2-fold increase in cardiovascular event risk, mirroring observations from CAR T-cell therapy in which more severe CRS is associated with greater cardiotoxicity. 4 , 5 Together, these findings reinforce the need for close hemodynamic and cardiac monitoring during episodes of significant immune activation. Further research is needed to establish evidence-based surveillance protocols for early detection and management of cardiovascular toxicity in this setting.

Established cardiovascular disease was present at baseline in 26% (n = 147) of the cohort, reflecting the growing inclusion of patients with substantial comorbidities undergoing advanced cancer therapies. Although the cumulative incidence of cardiovascular events during TCE therapy was 10.4%, baseline coronary artery disease was independently associated with a higher risk of subsequent cardiovascular events, including acute coronary syndrome. These findings highlight the importance of thorough cardiovascular assessment and optimization in patients with preexisting coronary artery disease before and throughout TCE therapy.

Study limitations

First, the cohort was drawn from 2 cancer centers, which may limit generalizability. Second, analyses were restricted to on-treatment cardiovascular events; therefore, we cannot comment on longer-term cardiovascular effects associated with TCE therapy. Third, because TCE dosing schedules varied and the study was retrospective, inflammatory and cardiac biomarkers were measured inconsistently, limiting our ability to assess their temporal relationship with cardiovascular events or to detect subclinical myocardial injury or inflammation. Fourth, this study evaluated TCE-related cardiovascular complications over a 10-year period during which treatment protocols, dosing schedules, premedication, and supportive care strategies evolved. Newly approved TCEs and improvements in monitoring and management of immune-related toxicities also may have influenced cardiovascular outcomes over the study period.

Conclusions

In summary, this study provides the first detailed characterization of cardiovascular toxicity during TCE therapy in a large real-world cohort. Although overall event rates were modest, preexisting coronary artery disease and development of grade ≥2 CRS and/or ICANS identified patients at substantially higher cardiovascular risk. These events were, in turn, associated with higher mortality, underscoring the clinical relevance of early recognition and coordinated cardio-oncology care. As TCE use continues to expand, prospective studies are needed to refine risk stratification and define evidence-based surveillance and management strategies.

COMPETENCY IN MEDICAL KNOWLEDGE: In patients receiving TCE therapies, baseline coronary artery disease and development of grade ≥CRS and/or ICANS identify those at heightened cardiovascular risk; cardiovascular events are significantly associated with higher subsequent mortality. Clinicians should incorporate targeted cardiovascular assessment and closer monitoring in patients with preexisting coronary disease, prior anthracycline exposure, or grade ≥2 CRS and/or ICANS to facilitate timely detection and management of cardiotoxicity.

TRANSLATIONAL OUTLOOK: Future prospective studies are needed to establish standardized surveillance protocols and determine whether tailored preventive or therapeutic strategies can improve outcomes in patients treated with TCE therapy.

Funding Support and Author Disclosures

Dr Nohria is supported by the Catherine Goff Fitch Fund and the Khoury Fund at Brigham and Women’s Hospital. Dr Bianchi is partially funded by a National Institutes of Health/National Cancer Institute K08CA245100 award. Dr Nohria receives research support from Bristol Myers Squibb; consulting fees from AstraZeneca, Teledoc, and Takeda Oncology; and speaker fees from MLI Education. Dr Itzhaki Ben Zadok receives advisory boards honoraria from Pfizer and Medison. Dr Bianchi has received honoraria for speaking engagements from Prothena and Pfizer Australia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Footnotes

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center .

Appendix

For supplemental figures and tables, please see the online version of this paper.

Appendix

Supplemental Material

References

1. Albayrak G., Wan P.K.T., Fisher K., Seymour L.W. T cell engagers: expanding horizons in oncology and beyond. Br J Cancer. 2025;133(9):1241–1249. doi: 10.1038/s41416-025-03125-y.

2. Géraud A., Hueso T., Laparra A., et al. Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review. Eur J Cancer. 2024;205 doi: 10.1016/j.ejca.2024.114075.

3. Palaskas N., Lopez-Mattei J., Durand J.B., Iliescu C., Deswal A. Immune checkpoint inhibitor myocarditis: pathophysiological characteristics, diagnosis, and treatment. J Am Heart Assoc. 2020;9(2) doi: 10.1161/JAHA.119.013757.

4. Mahmood S.S., Riedell P.A., Feldman S., et al. Biomarkers and cardiovascular outcomes in chimeric antigen receptor T-cell therapy recipients. Eur Heart J. 2023;44(22):2029–2042. doi: 10.1093/eurheartj/ehad117.

5. Itzhaki Ben Zadok O., Simitsis P., Jacobson C., et al. Cardiovascular complications and their association with short- and long-term outcomes in patients with multiple myeloma and lymphoma undergoing chimeric antigen receptor T-cell therapy. Circulation. 2024;150(22):1815–1817. doi: 10.1161/CIRCULATIONAHA.124.070432.

6. Sayed A., Munir M., Ghazi S.M., et al. Cardiovascular toxicities associated with bispecific T-cell engager therapy. J Immunother Cancer. 2024;12(2) doi: 10.1136/jitc-2023-008518.

7. Lyon A.R., López-Fernández T., Couch L.S., et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS): developed by the task force on cardio-oncology of the European Society of Cardiology (ESC) Eur Heart J. 2022;43(41):4229–4361. doi: 10.1093/eurheartj/ehac244.

8. Herrmann J., Lenihan D., Armenian S., et al. Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement. Eur Heart J. 2022;43(4):280–299. doi: 10.1093/eurheartj/ehab674.

9. Rao S.V., O’Donoghue M.L., Ruel M., et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the management of patients with acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2025;85(12):2135–2237. doi: 10.1016/j.jacc.2024.11.009.

10. Kleindorfer D.O., Towfighi A., Chaturvedi S., et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52(7):e364–e467. doi: 10.1161/STR.0000000000000375.

11. Lee D.W., Santomasso B.D., Locke F.L., et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transpl. 2019;25(4):625–638. doi: 10.1016/j.bbmt.2018.12.758.

12. Putter H., Fiocco M., Geskus R.B. Tutorial in biostatistics: competing risks and multi-state models. Stat Med. 2007;26(11):2389–2430. doi: 10.1002/sim.2712.

13. Salem J.E., Manouchehri A., Moey M., et al. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018;19(12):1579–1589. doi: 10.1016/S1470-2045(18)30608-9.

14. Itzhaki Ben Zadok O., Levi A., Divakaran S., Nohria A. Severe vs nonsevere immune checkpoint inhibitor-induced myocarditis: contemporary 1-year outcomes. JACC CardioOncol. 2023;5(6):732–744. doi: 10.1016/j.jaccao.2023.09.004.

Associated Data

Supplementary Materials

Supplemental Material