# New Blood Cancer Immunotherapies and Their Effects on the Heart: What Patients Should Know

This narrative review examines the cardiovascular (heart and blood vessel) toxicities of two powerful new blood-cancer immunotherapies: chimeric antigen receptor T-cell (CAR-T) therapy and bispecific T-cell engagers (BiTEs). The authors report that both treatments can cause a wide range of heart-related side effects. These range from common drops in blood pressure and fast heart rate to rare but severe events. The severe events include dangerous heart rhythms, weakened heart pumping, heart attack, and cardiogenic shock. Cardiogenic shock is when the heart cannot pump enough blood for the body's needs. A key finding is that most cardiovascular events with BiTEs appear to occur independently of cytokine release syndrome (CRS). CRS is a massive immune-system overreaction. In contrast, CAR-T-related heart toxicity is closely tied to CRS. The authors call for proactive heart-risk assessment before treatment. The authors call for serial monitoring of cardiac biomarkers, which are blood tests that signal heart stress or damage. The authors call for timely immunosuppressive treatment, mainly with tocilizumab. The authors propose a phase-specific clinical management algorithm.

# New Blood Cancer Immunotherapies and Their Effects on the Heart: What Patients Should Know

## Table of Contents

- Key Points
- Background: Why This Research Matters
- The Two Therapy Types: CAR-T Cells and Bispecific T-Cell Engagers
- How These Therapies May Harm the Heart
- The Range of Cardiovascular Side Effects
- Findings from Major Clinical Trials
- Evidence from Dedicated Observational Studies and Meta-Analyses
- What This Means for Patients
- Limitations: What the Research Could Not Prove
- Recommendations and Actionable Advice
- Frequently Asked Questions
- Source Information

## Key Points

- CAR-T and BiTE therapies can cause heart side effects ranging from low blood pressure and fast heart rate to rare severe events like dangerous rhythms, weakened pumping, heart attack, and cardiogenic shock.
- With CAR-T therapy, heart toxicity is closely tied to cytokine release syndrome (CRS); with BiTEs, most cardiovascular events appear to occur independently of CRS.
- Before treatment, a thorough cardiovascular assessment is recommended; during treatment, monitor blood pressure, heart rate, oxygen, and cardiac biomarkers; after treatment, continue monitoring for late-onset problems.
- Tocilizumab is the primary immunosuppressive intervention to mitigate CRS-driven injury, and electrolyte levels should be checked and corrected to reduce arrhythmia risk.
- Long-term cardiovascular outcomes are poorly characterized, validated surveillance protocols are lacking, and prospective studies are needed, especially for BiTE-associated heart toxicity.

## Background: Why This Research Matters

New immunotherapy treatments have changed the outlook for people with blood cancers. The two most important classes are chimeric antigen receptor T-cell (CAR-T) therapy and bispecific T-cell engagers (BiTEs). These treatments have produced response rates that older approaches could not achieve. In some patients, they have produced lasting remissions.

As more patients receive these therapies, doctors have learned that the treatments can affect the heart and blood vessels. This has created a new area of medicine called cardio-oncology, which focuses on heart health in people receiving cancer treatment.

Many patients who receive CAR-T or BiTE therapy already have other health problems and existing heart risk factors. Some have previously received chemotherapy drugs that can damage the heart. This makes the challenge of treating the cancer while protecting the heart even more complex.

Cardio-oncology has traditionally focused on heart problems caused by standard chemotherapy. The best-known example is heart damage from anthracyclines, a common class of chemotherapy drugs. More recently, attention has turned to heart inflammation and artery disease caused by immune checkpoint inhibitors, another type of immunotherapy.

The heart effects of CAR-T and BiTE therapies represent a distinct and fast-moving new frontier. This area needs its own dedicated research. CAR-T therapy has been linked to a unique pattern of heart complications that are closely tied to cytokine release syndrome (CRS) and widespread inflammation.

Early observations documented acute heart events during CAR-T cell expansion. These events included heart rhythm problems, weakened left ventricular pumping, and unstable blood pressure. The CARdio-Tox prospective study found patterns of both systolic and diastolic changes over time. These changes can evolve during and after the CAR-T cell infusion.

Beyond the acute phase, newer evidence suggests that CAR-T therapy may trigger lasting blood vessel inflammation. This raises concern about faster artery hardening and long-term heart effects that extend well beyond the initial treatment period. As patients live longer after these treatments, late-onset heart problems such as heart failure (HF), coronary artery disease (CAD), and blood vessel dysfunction require systematic long-term monitoring.

In contrast, the heart toxicity profile of BiTEs is less well described. Unlike CAR-T therapy, a large share of heart-related side effects with BiTEs appear to occur independently of CRS. This suggests distinct and incompletely understood mechanisms that deserve dedicated study. Comprehensive frameworks that combine the heart risks of both therapy classes are currently lacking.

This review aims to provide a systematic appraisal of the mechanisms, clinical range, and management of heart toxicities linked to CAR-T cells and BiTEs in blood cancers. The authors synthesize current evidence and identify knowledge gaps. Their ultimate goal is to inform integrated cardio-oncology frameworks for this emerging treatment frontier.

Unlike earlier cardio-oncology reviews that focused on traditional chemotherapy, immune checkpoint inhibitors, or CAR-T therapy alone, this review provides a direct side-by-side comparison between CAR-T cells and BiTEs. The work also bridges mechanistic insights with practical care. It incorporates new risk stratification tools, such as the CART-7 score, and proposes a phase-specific clinical algorithm covering baseline evaluation, acute monitoring, and long-term surveillance.

## The Two Therapy Types: CAR-T Cells and Bispecific T-Cell Engagers

CAR-T cell therapy and BiTEs are two distinct but related approaches to T-cell-redirecting immunotherapy. Both have transformed the management of blood cancers over the past decade. Both classes use the killing power of T lymphocytes (a type of white blood cell) against tumor-associated antigens (markers on cancer cells). However, they differ substantially in how they are made, how they behave in the body, and their toxicity profiles.

### CAR-T Cell Therapy

CAR-T cell therapy involves genetically engineering a patient's own T cells outside the body. The modified T cells express a chimeric antigen receptor, a synthetic construct that combines an extracellular antigen-binding domain with intracellular signaling components. When the receptor binds its target antigen, it drives T-cell activation and cytotoxicity.

The first FDA-approved product, tisagenlecleucel, was approved in 2017 for pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Since then, the field has expanded considerably. Multiple approved products now cover indications across B-cell lymphomas, multiple myeloma, and acute lymphoblastic leukemia.

CAR-T constructs are commonly classified by generation, reflecting progressive refinements in their intracellular signaling architecture:

-
**First-generation CAR-T** incorporated extracellular domains (antibody-derived single-chain variable fragments) engineered to recognize and bind directly to the CD19 protein found on the surface of B cells. These resulted in limited T-cell proliferation and persistence.
-
**Second-generation constructs** — which include the majority of currently approved products — integrated a single costimulatory domain (CD28 or 4-1BB). This substantially improved T-cell expansion, persistence, and antitumor activity.
-
**Third-generation CARs** combined multiple costimulatory domains, though without consistent evidence of superior clinical efficacy over second-generation designs.
-
**Fourth- and fifth-generation constructs** have introduced additional functional enhancements. These include the capacity to secrete proinflammatory cytokines or engage innate immune components, broadening antitumor activity and enabling recognition of a wider spectrum of tumor-associated antigens.

Target selection is another key dimension of CAR-T classification. CD19 remains the most extensively studied and clinically used target, followed by B-cell maturation antigen (BCMA) in multiple myeloma. Additional targets under active investigation include CD20, CD22, and CD138, among others.

To overcome limitations such as antigen downregulation and immune evasion, multi-target CAR-T constructs capable of recognizing more than one antigen at once are under development. Complementary strategies include:

- Combination with immune checkpoint inhibitors to enhance CAR-T persistence, as demonstrated in patients with malignant pleural disease treated with mesothelin-directed CAR-T and pembrolizumab.
- Genetic disruption of inhibitory pathways such as PD-1/PD-L1 using CRISPR/Cas9 editing.
- Adaptor CAR-T (AdCAR-T) platforms that use intermediary molecules to redirect a universal CAR construct toward different tumor antigens, increasing therapeutic flexibility.

### Bispecific T-Cell Engagers

Unlike CAR-T therapy, BiTEs are recombinant bispecific antibody constructs. They bind simultaneously to a tumor-associated antigen on malignant cells and to CD3ε on endogenous T lymphocytes. This physically bridges the two cell types and induces polyclonal T-cell activation and tumor cell lysis, independent of major histocompatibility complex presentation.

A critical practical advantage over CAR-T therapy is that BiTEs are "off-the-shelf" agents. They do not require individualized T-cell manufacturing outside the body, enabling more immediate clinical availability.

Blinatumomab, a CD19×CD3 bispecific construct, was the first BiTE to receive regulatory approval. The FDA granted approval in 2014 for relapsed or refractory B-cell acute lymphoblastic leukemia. The class has since expanded rapidly, with multiple agents receiving FDA or EMA approval for blood cancers, with indications spanning B-cell lymphomas and multiple myeloma.

Approved agents for lymphoma include epcoritamab (CD20×CD3) and glofitamab (CD20×CD3). The multiple myeloma landscape includes teclistamab, elranatamab, and talquetamab, targeting BCMA×CD3, BCMA×CD3, and GPRC5D×CD3 respectively. Mosunetuzumab has received approval for follicular lymphoma.

Administration schedules typically involve an initial step-up dosing phase, designed to reduce the risk of cytokine release syndrome, followed by weekly or biweekly maintenance dosing. Extended intervals are under investigation in responding patients.

Unlike CAR-T therapy, which is a single intervention with a potentially durable effect, BiTEs require continuous or intermittent administration. This difference has distinct implications for cumulative toxicity and long-term heart monitoring.

The primary mechanism of off-tumor toxicity in BiTE therapies relates to antigen expression on normal tissues. This can lead to on-target, off-tumor organ damage. Several strategies to improve selectivity are under investigation, including prodrug BiTE constructs that are selectively activated within the tumor microenvironment and dual tumor-specific binding domain designs.

## How These Therapies May Harm the Heart

CAR-T cell therapy and BiTE therapy have both been associated with cardiovascular adverse events, contributing to an increased overall heart risk profile in treated patients. Three principal mechanisms have been proposed to explain CAR-T-related heart toxicity: direct heart muscle damage, systemic inflammatory responses, and antigen cross-reactivity.

### Direct Heart Muscle Damage (On-Target, Off-Tumor Toxicity)

The first mechanism involves direct toxic effects mediated by engineered T cells that recognize antigens expressed on heart muscle tissue. This phenomenon is classified as "on-target, off-tumor" toxicity. It occurs when the intended target antigen is also expressed on normal heart tissue, rather than being truly tumor-specific. This makes heart muscle cells susceptible to CAR-T-mediated cytotoxicity.

This represents a fundamental challenge in CAR-T therapy. Most tumor-associated antigens are not truly tumor-specific. They are self-antigens expressed at higher levels on malignant cells. The CAR-T cells function exactly as designed — they successfully recognize their target antigen — but cause collateral damage to healthy organs that share expression of that antigen.

However, clinically obvious on-target, off-tumor heart toxicity with currently approved CD19- and BCMA-directed CAR-T products is extremely rare. These antigens are not meaningfully expressed on heart tissue. This mechanism is therefore primarily a theoretical concern for next-generation constructs targeting novel antigens with broader tissue expression profiles.

### Cytokine Release Syndrome (CRS)

The second and clinically most relevant mechanism is cytokine release syndrome (CRS). CRS is a systemic inflammatory response resulting from the interaction between CAR-T cells and tumor cells within the tumor microenvironment. It is classified as an "on-target, on-tumor" adverse effect.

This interaction triggers a cascade of proinflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nitric oxide. These drive systemic inflammation and immune activation. Among these, IL-6 plays a central and well-characterized role in CRS-associated heart injury.

Clinically, CRS typically appears 2–3 days after infusion. Onset may occur within hours or be delayed up to 10–15 days. CRS presents with fever, low blood pressure, fast heart rate, and low oxygen levels. The overall incidence of CRS ranges from 35% to 93%. Severe cases occur in 1–47% of CAR-T recipients.

Serious heart events associated with CRS include:

- Atrial fibrillation (AF, an irregular heart rhythm)
- Ventricular tachycardia (a fast, dangerous heart rhythm)
- Cardiac arrest
- Heart failure
- Capillary leak syndrome (fluid leaking from small blood vessels into tissues)

Approximately 10–15% of patients may develop cardiomyopathy (heart muscle disease) in the context of high-grade CRS. Heart events occur in up to 20% of patients with high-grade CRS. Both the American Society for Transplantation and Cellular Therapy and the Common Terminology Criteria for Adverse Events have established grading systems for CRS severity. These are essential for guiding treatment.

CRS may also involve the central nervous system, resulting in a condition known as immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS typically occurs 4–10 days after infusion. It is characterized by varied neurologic symptoms, including encephalopathy (brain dysfunction), delirium, aphasia (difficulty with language), tremor, motor dysfunction, and, in severe cases, seizures and cerebral edema (brain swelling). Recognizing ICANS is critical, as it carries distinct treatment and prognostic implications compared with systemic CRS alone.

While IL-6 is central to CRS, heart muscle and blood vessel injury during CRS results from a synergistic cytokine network. This network involves interleukin-1 beta (IL-1β), TNF-α, interferon gamma (IFN-γ), and interleukin-8 (IL-8).

TNF-α and IFN-γ act synergistically with IL-6 trans-signaling to disrupt the endothelial barrier (the lining of blood vessels) and upregulate cell adhesion molecules. Local IL-8 production recruits and activates neutrophils (a type of immune cell). TNF-α and IL-1β downregulate endothelial nitric oxide synthase and induce endothelial apoptosis (programmed cell death of blood vessel lining cells).

Together, these pathways drive systemic capillary leak, microvascular thrombosis (clotting in small blood vessels), and refractory hypotension (blood pressure that does not respond to treatment). TNF-α and IL-1β directly blunt the responsiveness of heart muscle cells to beta-adrenergic signals. This disrupts intracellular calcium handling and causes acute contractile dysfunction (weakened heart pumping).

At the same time, IFN-γ amplifies inflammatory signaling, promotes mitochondrial reactive oxygen species production, and triggers opening of the mitochondrial permeability transition pore. These changes further stress heart muscle cells.

### Antigen Cross-Reactivity (Off-Target, Off-Tumor Effects)

The third proposed mechanism may be attributed to a lack of selectivity, especially with first-generation CAR-T. It is an "off-target, off-tumor" effect. In this case, CAR-T cells recognize antigens that were not intended as targets — antigens expressed on normal tissues but not on tumor cells, including heart muscle.

This can arise through several distinct pathways:

-
**Molecular mimicry**, whereby the CAR or T-cell receptor recognizes structurally similar epitopes (antigen fragments) on unrelated proteins.
-
**Antigen-independent activation** through interactions between CAR constructs and innate immune cells.
-
**Tonic signaling**, in which constitutive CAR activation occurs in the absence of antigen engagement.

The risk is particularly high when using affinity-enhanced or modified T-cell receptors, which may have broader peptide recognition than naturally occurring receptors. This kind of cross-reactivity and its potentially dangerous effects are well documented in the current literature and demonstrated using different genetic technologies.

One example is the cross-reaction of a structurally similar peptide derived from titin, a sarcomeric protein expressed in heart muscle, with affinity-enhanced T-cell receptors originally designed to target MAGE-A3. This caused fatal cardiogenic shock. While such direct heart toxicity remains rare with current CD19- and BCMA-directed CAR-T products, it underscores the potential for off-target effects when targeting antigens with tissue expression beyond the tumor.

While this mechanism has been less commonly implicated in current commercial CAR-T products, it remains a theoretical concern as CAR-T therapy expands to target novel antigens and solid tumors.

### How BiTE Heart Toxicity Differs

In contrast, the heart toxicity mechanisms of BiTE therapy are less well characterized and appear to differ in important aspects from those of CAR-T. CRS remains a recognized driver of heart injury with BiTEs. However, a particularly notable finding from pharmacovigilance data (safety monitoring data) concerns BiTE therapy. The majority of heart adverse events associated with BiTE therapy occur independently of CRS.

This suggests that distinct and incompletely understood pathophysiological mechanisms are involved beyond cytokine-mediated injury. Whether these reflect direct endothelial or heart muscle effects of sustained T-cell activation, immune complex deposition, or other mechanisms remains to be defined.

## The Range of Cardiovascular Side Effects

CAR-T and BiTE therapies are associated with a broad and heterogeneous spectrum of cardiovascular adverse events (CVAEs). However, the currently available evidence remains partly inconsistent. This is because of the predominance of retrospective studies, heterogeneous patient populations, and variability across meta-analyses.

These immune-based therapies may induce:

- Acute hemodynamic instability (unstable blood pressure and circulation)
- Rhythm disturbances
- Myocardial injury (heart muscle damage)
- Ischemic and thrombotic complications (reduced blood flow and clots)
- Pericardial involvement (effects on the sac around the heart)
- Other heart toxicities

These events frequently occur in association with CRS.

## Findings from Major Clinical Trials

The pivotal clinical trials investigating CAR-T and BiTE therapies primarily reported heart toxicities in the context of CRS. Low blood pressure and fast heart rate were the most frequently observed manifestations.

### The ZUMA-1 Trial (Axicabtagene Ciloleucel)

In the ZUMA-1 trial evaluating axicabtagene ciloleucel (axi-cel), the principal heart adverse events were low blood pressure and fast heart rate. The study enrolled 111 patients, including 77 with diffuse large B-cell lymphoma and 24 with primary mediastinal B-cell lymphoma or transformed follicular lymphoma.

Among the 111 patients who received axi-cel, all experienced adverse events. These were grade 3 or higher in 95% of cases. CRS occurred in 93% of patients, with grade 3 or higher CRS reported in 13% (9% grade 3, 3% grade 4, and 1% grade 5). Low blood pressure was observed in 59% of patients with CRS. Vasopressor support (medication to raise blood pressure) was required in 17% of all treated patients.

### The JULIET Trial (Tisagenlecleucel)

Similarly, the JULIET trial investigating tisagenlecleucel in relapsed or refractory diffuse large B-cell lymphoma reported a substantial incidence of CRS-related hemodynamic complications. A total of 93 patients received the infusion. Twenty-two percent developed grade 3–4 CRS requiring intensive supportive measures, including:

- Oxygen supplementation (24%)
- Endotracheal intubation (7%)
- High-dose vasopressors (6%)
- Dialysis (5%)

Low blood pressure of any grade occurred in 26% of patients. Fast heart rate was reported in 11%.

### The KarMMa Study (Idecabtagene Vicleucel)

Comparable findings emerged from the Phase 2 KarMMa study evaluating idecabtagene vicleucel in relapsed or refractory multiple myeloma. Hemodynamic adverse events were again frequently observed, with low blood pressure occurring in 16% of patients.

In addition, electrolyte abnormalities that could predispose to arrhythmias were commonly reported:

- Low potassium (hypokalemia): 35%
- Low phosphate (hypophosphatemia): 30%
- Low calcium (hypocalcemia): 27%
- Low magnesium (hypomagnesemia): 23%

However, specific data regarding arrhythmic events were not reported.

### BiTE Trials: TOWER, BLAST, and Teclistamab

Clinical trials investigating BiTE therapies have similarly described low blood pressure and fast heart rate as the most common heart adverse events.

In the Phase 3 TOWER trial evaluating blinatumomab versus chemotherapy in advanced acute lymphoblastic leukemia, 267 patients received blinatumomab. Low blood pressure occurred in 12% of patients and fast heart rate in 6.7%. Isolated cases of atrial fibrillation and atrial flutter were also documented. Consistent findings with similar incidences were reported in the Phase 2 BLAST study on blinatumomab.

In contrast, the Phase 1–2 study evaluating teclistamab in relapsed or refractory multiple myeloma suggested a lower incidence of clinically significant hemodynamic toxicity. Although 72.1% of the 165 treated patients developed CRS-related symptoms, vasopressor support was required in only one patient. This indicates a comparatively limited heart impact in terms of severe low blood pressure events.

As reported before, these mechanisms and their real pathophysiology, as well as their incidence, remain uncertain. Prospective studies are needed.

## Evidence from Dedicated Observational Studies and Meta-Analyses

Beyond pivotal trials, dedicated observational studies and meta-analyses have provided a more granular characterization of the heart toxicity profiles of both therapy classes.

In a comprehensive review, Mara and colleagues described the main cardiovascular manifestations. These included fast heart rate and troponin elevation, a blood marker of heart muscle damage. These included reduction in left ventricular ejection fraction (LVEF, a measure of how well the heart pumps). These included decompensated heart failure with pulmonary edema (fluid in the lungs). These included new-onset arrhythmias and severe low blood pressure progressing to shock.

More recent quantitative data from the meta-analysis by Maleki and colleagues reported high incidences of cardiovascular adverse events, largely associated with CRS of grade 2 or higher. Importantly, patients experiencing cardiovascular adverse events showed a greater decline in LVEF. This reinforces the need for structured heart monitoring during CAR-T therapy.

However, real-world data appear to show variation in these findings. The available evidence remains partly inconsistent because of the predominance of retrospective studies, heterogeneous patient populations, and variability across meta-analyses.

## What This Means for Patients

These findings have direct relevance for anyone considering or receiving CAR-T or BiTE therapy. The heart is not the primary target of these treatments, but it can be affected. The risk is real and, in some cases, serious.

The good news is that most heart-related side effects are manageable when detected early. Low blood pressure and fast heart rate are common and often respond to supportive care. Severe events such as dangerous heart rhythms, weakened heart pumping, heart attack, and cardiogenic shock are less common but require immediate attention.

A key difference between the two therapy classes matters for monitoring. With CAR-T therapy, heart problems are closely tied to CRS. This means that when CRS is well controlled, heart risk tends to fall as well. With BiTEs, a substantial proportion of heart events occur independently of CRS. This means that even patients without CRS still need careful heart monitoring.

Patients who already have heart disease or heart risk factors may face higher risk. Prior treatment with cardiotoxic chemotherapy adds to this risk. This is why baseline heart assessment before starting therapy is so important.

The authors emphasize that effective management requires three things:

1. Proactive baseline risk stratification (assessing heart risk before treatment starts)
1. Serial cardiac biomarker monitoring (repeated blood tests during and after treatment)
1. Timely immunosuppressive intervention — primarily tocilizumab — to mitigate CRS-driven injury

## Limitations: What the Research Could Not Prove

Despite the rapid clinical expansion of these therapies, critical gaps remain. The authors are explicit about what is still unknown.

Long-term cardiovascular outcomes are poorly characterized. Most of the evidence comes from the acute treatment period. Little is known about heart health years after treatment.

Validated surveillance protocols are lacking. There is no universally agreed-upon schedule for heart monitoring in these patients. Different centers may monitor differently, which makes it hard to compare results.

Cardiovascular endpoints are rarely included in pivotal trials. The major trials that led to drug approvals focused primarily on cancer response and CRS. They did not systematically collect detailed heart data. This limits what can be concluded about heart risk from those trials.

The currently available evidence remains partly inconsistent. This is because of the predominance of retrospective studies, heterogeneous patient populations, and variability across meta-analyses.

The mechanisms of BiTE-associated heart toxicity are less well characterized than those of CAR-T. Whether the CRS-independent heart events reflect direct endothelial or heart muscle effects of sustained T-cell activation, immune complex deposition, or other mechanisms remains to be defined. Prospective studies are needed.

Some mechanisms, such as on-target, off-tumor heart toxicity and off-target, off-tumor cross-reactivity, remain primarily theoretical concerns for current approved products. They are more relevant to next-generation constructs targeting novel antigens with broader tissue expression profiles.

## Recommendations and Actionable Advice

Based on this review, the authors propose a phase-specific clinical algorithm for managing heart risk in patients receiving CAR-T or BiTE therapy. This algorithm covers three phases: baseline evaluation, acute monitoring, and long-term surveillance.

### Before Treatment: Baseline Evaluation

1. Undergo a thorough cardiovascular assessment before starting therapy. This should include a review of your heart history, physical examination, and baseline heart tests.
1. Tell your care team about any prior chemotherapy, especially anthracyclines, and any existing heart conditions.
1. Discuss your individual heart risk with your oncology and cardiology teams. Tools such as the CART-7 score may help estimate risk.
1. Ensure your blood pressure, heart rhythm, and heart pumping function are documented as a baseline for future comparison.

### During Treatment: Acute Monitoring

1. Expect close monitoring of blood pressure, heart rate, and oxygen levels, especially in the first days after CAR-T infusion or during BiTE step-up dosing.
1. Serial cardiac biomarker monitoring (such as troponin) can help detect heart stress or damage early.
1. If CRS develops, it should be treated promptly. Tocilizumab is the primary immunosuppressive intervention to mitigate CRS-driven injury.
1. Report symptoms such as chest pain, palpitations, shortness of breath, swelling, or dizziness immediately to your care team.
1. Electrolyte levels should be checked and corrected, as low potassium, phosphate, calcium, and magnesium can predispose to heart rhythm problems.

### After Treatment: Long-Term Surveillance

1. Continue heart monitoring after the acute treatment period. Late-onset heart problems such as heart failure, coronary artery disease, and blood vessel dysfunction can occur.
1. Because BiTEs require continuous or intermittent administration, cumulative toxicity and long-term heart surveillance have distinct implications compared with the single intervention of CAR-T therapy.
1. Maintain regular follow-up with a cardio-oncology team when available.
1. Discuss any new heart symptoms with your care team, even months or years after treatment.

The authors conclude that integrated cardio-oncology care is essential. This care should be based on baseline cardiovascular assessment, longitudinal monitoring, early recognition of cardiovascular complications, and multidisciplinary management. This approach aims to optimize both heart and cancer outcomes in patients receiving CAR-T and BiTE therapies.

## Frequently Asked Questions

### What heart side effects can CAR-T therapy and BiTE therapy cause?

Both treatments can cause a wide range of heart-related side effects. Common ones include drops in blood pressure and fast heart rate. Rare but severe events include dangerous heart rhythms, weakened heart pumping, heart attack, and cardiogenic shock, which is when the heart cannot pump enough blood for the body's needs. These events often occur with cytokine release syndrome.

### How do heart risks differ between CAR-T therapy and BiTE therapy?

With CAR-T therapy, heart toxicity is closely tied to cytokine release syndrome (CRS), a massive immune-system overreaction. With BiTE therapy, a key finding is that most cardiovascular events appear to occur independently of CRS. This means that even patients who do not develop CRS still need careful heart monitoring during BiTE treatment.

### What is cytokine release syndrome (CRS) and how does it affect the heart?

CRS is a systemic inflammatory response that typically appears 2–3 days after CAR-T infusion, though onset may occur within hours or be delayed up to 10–15 days. It presents with fever, low blood pressure, fast heart rate, and low oxygen levels. Serious heart events linked to CRS include atrial fibrillation, ventricular tachycardia, cardiac arrest, heart failure, and capillary leak syndrome.

### What heart monitoring is recommended before, during, and after treatment?

Before treatment, a thorough cardiovascular assessment is recommended, including heart history, physical examination, and baseline heart tests. During treatment, expect close monitoring of blood pressure, heart rate, and oxygen levels, plus serial cardiac biomarker monitoring such as troponin. After treatment, continue heart monitoring because late-onset problems like heart failure and coronary artery disease can occur.

### What should I report to my care team during treatment?

Report symptoms such as chest pain, palpitations, shortness of breath, swelling, or dizziness immediately to your care team. Also tell them about any prior chemotherapy, especially anthracyclines, and any existing heart conditions. Electrolyte levels should be checked and corrected, as low potassium, phosphate, calcium, and magnesium can predispose to heart rhythm problems.

### What treatments are used if heart problems or CRS develop?

If CRS develops, it should be treated promptly. Tocilizumab is the primary immunosuppressive intervention to mitigate CRS-driven injury. Supportive care may include oxygen supplementation, vasopressors to raise blood pressure, and other measures as needed. The authors call for timely immunosuppressive treatment and propose a phase-specific clinical management algorithm.

### What does the research not yet prove about long-term heart effects?

Long-term cardiovascular outcomes are poorly characterized, as most evidence comes from the acute treatment period. Validated surveillance protocols are lacking, and cardiovascular endpoints are rarely included in pivotal trials. The mechanisms of BiTE-associated heart toxicity are less well characterized than those of CAR-T, and prospective studies are needed to clarify them.

### When should a patient starting CAR-T or BiTE therapy for blood cancer seek a second opinion?

A second opinion is reasonable before starting CAR-T or BiTE therapy, because baseline heart assessment shapes the whole treatment plan. Prior chemotherapy, especially anthracyclines, and existing heart conditions raise heart risk, and tools such as the CART-7 score may help estimate it. An independent review can confirm whether baseline heart tests, biomarker monitoring, and electrolyte checks are planned, and whether tocilizumab is available for CRS-driven injury. Because BiTE heart events often occur without CRS, monitoring plans differ between the two therapies. Diagnostic Detectives Network provides independent expert second opinions.

## Source Information

**Original article title:** The New Cardio-Oncology Frontier in Hematologic Cancers: Cardiovascular Toxicities of CAR-T Cells and Bispecific T-Cell Engagers.

**Authors:** Tedeschi A, Pasini N, Talassi M, Barocelli F, Fabiani I, Quagliariello V, Maurea N, Canale ML, Oliva S, Niccoli G, Aschieri D.

**Publication details:** Journal of Clinical Medicine (J. Clin. Med.), 2026, volume 15, article 6371. Published 18 August 2026. DOI: 10.3390/jcm15166371. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) license.

**Article type:** Narrative review.

*This patient-friendly article is based on peer-reviewed research.*


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