Toxicities per treatment type

Anthracycuines

Agent

Main oncologic / hematologic indications

Type of cardiotoxicity

Estimated risk

Doxorubicin (Adriamycin®, Caelyx® (pegylated liposomal)) Daunorubicin Epirubicin Idarubicin

Solid tumors:
breast cancer, ovarian cancer, lung cancer, gastrointestinal cancers, bone and soft-tissue sarcomas.

Hematologic malignancies:
Hodgkin and non-Hodgkin lymphoma, ALL, AML, multiple myeloma, neuroblastoma.

Dose-dependent, often irreversible myocardial damage.
Typically presents as dilated cardiomyopathy and HF.
Acute effects (rare): arrhythmias, transient LV dysfunction.
Pathophysiology: cardiomyocyte apoptosis, oxidative stress, topoisomerase IIβ inhibition, mitochondrial dysfunction.

Symptomatic CTRCD:

~1–5% at low–moderate cumulative doses.
Up to 5–20% or higher at high cumulative doses (e.g. doxorubicin >550 mg/m²).

Asymptomatic CTRCD:

20–40%

Mitoxantrone

Hematologic malignancies:
Acute myeloid leukemia (especially relapsed/refractory), non-Hodgkin lymphoma

Solid tumors:
metastatic castration-resistant prostate cancer.

Non-oncologic indications:
selected forms of multiple sclerosis.)

anthracycline-like myocardial injury:
Dose-dependent systolic dysfunction and HF.
Mechanistically similar to anthracyclines but less cardiotoxic per cumulative dose.

Generally lower than doxorubicin.
Commonly reported around 1–4% at standard cumulative doses.

Proposed Surveillance (ESC guidelines):

Of note: NTproBNP is not reimbursed in Belgium

Anthracycline equivalent dosis calculator: https://www.cancercalc.com/anthracycline.php

References

Henriksen, P. A. (2018). “Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention.” Heart, 104(12), 971–977.
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). European Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244
https://www.cancer.gov/about-cancer/treatment/drugs/

Anti-her2

Agent (commercial name)	Main oncologic indications	Type of cardiotoxicity	Estimated risk
Trastuzumab (Herceptin®)	HER2-positive (IHC 3+ or FISH+) breast cancer (early and metastatic). HER2-positive gastric, gastro-esophageal junction, and selected pulmonary cancers.	Predominantly LV systolic dysfunction (LVSD) Non–dose-dependent Often reversible after treatment interruption	Symptomatic CTRCD: 2–4% with anthracyclines <1% without anthracyclines Asymptomatic CTRCD: up to 10–15%
Pertuzumab (Perjeta®)	HER2-positive breast cancer (early and metastatic), in combination with trastuzumab and chemotherapy.
Trastuzumab emtansine (T-DM1) (Kadcyla®)	HER2-positive breast cancer in the (neo)adjuvant and metastatic setting after prior trastuzumab/taxane therapy.		LVEF decline: ~0.9% Symptomatic HF is uncommon
Trastuzumab deruxtecan (T-DXd) (Enhertu®)	HER2-positive metastatic breast cancer. HER2-low (IHC 2+, FISH−) and HER2 ultra-low (IHC 1+) metastatic breast cancer.		LVEF decline: ~4.2% Symptomatic HF is uncommon

Across all HER2-targeted therapies, the risk of cancer therapy–related cardiac dysfunction (CTRCD) is significantly increased when combined with or preceded by anthracycline therapy, emphasizing the importance of baseline cardiovascular risk stratification and cardiac monitoring.

Proposed Surveillance (ESC guidelines):

NTproBNP is not reimbursed in Belgium

References

Zamorano, J. L., et al. (2016). “2016 ESC Position Paper on cancer treatments and cardiovascular toxicity.” European Journal of Heart Failure, 19(1), 9–42.Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244
Seth L, Bhave A, Kollapaneni S, et al. Cardiotoxic Effects of Antibody Drug Conjugates vs Standard Chemotherapy in ERBB2-Positive Advanced Breast Cancer: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2025;8(11):e2540336. doi:10.1001/jamanetworkopen.2025.40336
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). European Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244
https://www.cancer.gov/about-cancer/treatment/drugs/

Antimetabolites

Agent	Main oncologic / hematologic indications	Type of cardiotoxicity	Estimated risk and risk factors
5-Fluorouracil (5-FU) Capecitabine	Gastrointestinal cancers: colorectal, gastric, pancreatic, esophageal cancer.Also used in (neo)adjuvant regimens for head and neck cancers.	Predominantly coronary vasospasm Angina, myocardial ischemia, myocardial infarction Atrial and ventricular arrhythmias	Any cardiac event: ~3–7% in most series (reported range 0.99–19.9%). Most frequent are ischemic events. Risk factors: pre-existing CAD, prior chest radiotherapy, renal insufficiency, dihydropyrimidine dehydrogenase (DPD) deficiency.
Cytarabine	Hematological indications: Acute myeloid leukemia (AML): induction and consolidation therapy. Other acute leukemias; Occasional use in lymphomas (e.g. intrathecal therapy).	Pericarditis Rare LV systolic dysfunction / cardiomyopathy	Pericarditis: <5%. Cardiomyopathy: rare, usually associated with high-dose regimens.
Methotrexate	Hematologic malignancies: Acute lymphocytic leukemia (ALL) (systemic and intrathecal), lymphomas (including primary CNS lymphoma). Solid tumors: osteosarcoma, head and neck cancers. Non-oncological indications: autoimmune disease and trophoblastic disease (low dose)	Pericarditis Rare LV systolic dysfunction / cardiomyopathy	Pericarditis / effusion: <5%, often dose-related. Cardiomyopathy: uncommon.

Proposed Surveillance for 5-Fluorouracil (5-FU) and Capecitabine (ESC guidelines):

No specific surveillance recommendations for cytarabine, methotrexate : consider surveillance strategies for other anticancer drugs that are given in combination.

References

Depetris I, Marino D, Bonzano A, Cagnazzo C, Filippi R, Aglietta M, Leone F. Fluoropyrimidine-induced cardiotoxicity. Crit Rev Oncol Hematol. 2018 Apr;124:1-10. doi: 10.1016/j.critrevonc.2018.02.002. Epub 2018 Feb 7. PMID: 29548480.
de Forni M, Armand JP. Cardiotoxicity of chemotherapy. Curr Opin Oncol. 1994 Jul;6(4):340-4. doi: 10.1097/00001622-199407000-00003. PMID: 7803534.
Weisfelner Bloom M et al. Cardio-Oncology and Heart Failure: a Scientific Statement From the Heart Failure Society of America. Journal of Cardiac Failure Volume 31, Issue 2 p 415-455February 2025

Other chemotherapy

Alkylating agents

Agents	Main oncologic / hematologic indications	Type of Cardiotoxicity	Approximate risk & notes
Cyclophosphamide, Ifosfamide	Hematologic indications: Lymphomas (e.g. CHOP) Leukemias high-dose conditioning before autologous or allogeneic HSCT Solid tumors: breast and ovarian cancer, • bone and soft-tissue sarcomas.	Acute/subacute CTR-CVT: Myocarditis Pericarditis / pericardial effusion • Cardiomyopathy / heart failure	High-dose regimens (>120–150 mg/kg): cardiotoxicity ~8–20% (adults), ~5% (children). HF: reported <5% up to 10–29%. Onset typically 48 h to 10 days after exposure.
Cisplatin	Testicular, head & neck, lung, bladder, ovarian, and GI cancers (esophageal, gastric).	Myocardial ischemia / MI (most common) Arrhythmias Hypertension Rare cardiomyopathy / heart failure	Considered low in monotherapy, higher (1-6%) when combined with other cardiotoxic agents (e.g. 5-FU).
Busulfan, Carmustine, Mitomycin, Melphalan	Hematologic indications: HSCT conditioning (busulfan, melphalan, carmustine). Multiple myeloma (high-dose melphalan). Solid tumors: Selected solid tumors (mitomycin in GI, carmustine in CNS tumors).	Often in high-dose settings for stem cell transplantation: Veno-occlusive disease Rare cardiomyopathy • Pericardial effusion	Overall cardiac toxicity ~1–5% in transplant settings; data mainly from case series.

Surveillance:

No specific recommendations
Consider surveillance driven by co-administered cardiotoxic agents.
Refer to cardio-oncology for cyclophosphamide/ifosfamide in patients with known CVD, high CV risk, or planned high-dose therapy.

Antimicrotubule Agents – Taxanes and Vinca Alkaloids

Agents	Main indications	Type of Cardiotoxicity	Approximate risk
Taxanes Paclitaxel, Docetaxel, Cabazitaxel	Breast, ovarian, lung, prostate, head & neck, gastric and esophageal cancers.	Bradycardia(often asymptomatic and transient). Arrhythmias less commonly, conduction abnormalities, myocardial ischemia, or heart failure.	Bradycardia: ~5–30% (often asymptomatic). Arrhythmias: <5%.
Vinca alkaloids Vincristine, Vinblastine	ALL, Hodgkin and non-Hodgkin lymphomas, multiple myeloma, pediatric solid tumors.	Rarely myocardial ischemia/infarction, arrhythmias, or hypertension.	Low cardiotoxicity risk: Cardiac events <1–2%.

Surveillance:

No specific recommendations
Consider surveillance driven by co-administered cardiotoxic agents.

Other Anticancer Agents

Agents / Class	Main indications	Type of Cardiotoxicity	Approximate risk & notes
Arsenic trioxide	Acute promyelocytic leukemia (APL).	QT prolongation → torsades de pointes	QTc >470 ms: 20–30%. QTc >500 ms: 10–15%. TdP very rare (<1%) with monitoring.
Bleomycin	Hodgkin lymphoma, testicular and germ-cell tumors.	Rare myocardial ischemia, Raynaud phenomenon	<1–2% in preexisting cardiovascular disease or with combination therapy.
Interferon-α	Myeloproliferative neoplasms, hairy cell leukemia; historical use in CML, melanoma, RCC.	Arrhythmias, cardiomyopathy, heart failure, ischemia, hypertension	Cardiac events 5–15%; Heart failure <5%.
Tretinoin (ATRA)	APL (with arsenic or chemotherapy).	Not common, but can contribute to “differentiation syndrome” which may involve heart failure and pericardial effusion.	Differentiation syndrome with cardiac manifestations <5%.
Amsacrine	Relapsed/refractory AML.	Arrhythmias, QT prolongation; rare HF	Arrhythmias 5–10%; Heart failure <1%.
HDAC inhibitors Romidepsin, Vorinostat	Cutaneous and peripheral T-cell lymphomas.	QT prolongation, arrhythmias	QT prolongation: 10–20% (romipdesin) QTc >500 ms: ~1–5%.
Somatostatin analogs Lanreotide, Octreotide	Neuroendocrine tumors; hormonal symptom control.	Bradycardia (usually asymptomatic)	Bradycardia 5–15%, <1–2% clinically significant.

Surveillance:

No specific recommendations

References

Batra A, Patel B, Addison D, Baldassarre LA, Desai N, Weintraub N, Deswal A, Hussain Z, Brown SA, Ganatra S, Agarwala V, Parikh PM, Fradley M, Ghosh A, Guha A. Cardiovascular safety profile of taxanes and vinca alkaloids: 30 years FDA registry experience. Open Heart. 2021 Dec;8(2):e001849. doi: 10.1136/openhrt-2021-001849. PMID: 34952868; PMCID: PMC8710909.
National Cancer Institute. (2023). “Cardiovascular toxicities of targeted cancer therapies.” NCI Drug Information Summaries.
Oracle. (2025). “Does Lanreotide (Somatostatin analogue) cause bradycardia and is it dangerous?”.FDA Drug Label for Somatuline Depot (lanreotide).
Mondal P, Jain D, Aronow WS, Frishman WH. Cardiotoxicity of Cancer Therapies. Cardiol Rev. 2019 Sep/Oct;27(5):230-235. doi: 10.1097/CRD.0000000000000239. PMID: 30433897.
Weisfelner Bloom M et al. Cardio-Oncology and Heart Failure: a Scientific Statement From the Heart Failure Society of America. Journal of Cardiac Failure Volume 31, Issue 2 p 415-455February 2025
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

Immune checkpoint inhibitors

Drug class / Agent	Main oncologic indications	ESC-aligned cardiotoxicity profile	Estimated risk
Anti-PD-1 / Anti-PD-L1 Nivolumab (Opdivo®) Pembrolizumab (Keytruda®) Atezolizumab (Tecentriq®) Durvalumab (Imfinzi®) Cemiplimab (Libtayo®) Avelumab (Bavencio®) Dostarlimab (Jemperli®)	Broad spectrum of solid tumours, including: Non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, urothelial carcinoma, head and neck cancers, MSI-H / dMMR colorectal and other GI cancers; hepatocellular carcinoma, cervical and endometrial cancer, cutaneous squamous cell carcinoma (Indication depends on tumour type and PD-1/PD-L1 status.)	Immune-mediated CTR-CVT: Myocarditis (often fulminant) Pericarditis Atrial and ventricular arrhythmias and conduction disorders Heart failure, including late non-inflammatory LV dysfunction	Myocarditis (all grades): ~0.06–1.14%. Case fatality rate: up to 30–50% despite low incidence. Higher incidence and severity in combination regimens. Other cardiac immune-related adverse events (irAEs) are similarly rare. Factors associated with high risk for cardiotoxicity: dual ICI therapy, combination ICI therapy with other cardiotoxic therapies, ICI-related non-CV events, prior CTRCD or CVD
Anti-CTLA-4 Ipilimumab (Yervoy®), Tremelimumab (Imjudo®)	Melanoma, hepatocellular carcinoma, renal cell carcinoma, selected GI and other solid tumors, often in combination with anti-PD-1 therapy.
Anti-LAG-3 Relatlimab (Opdualag® — fixed-dose combination with nivolumab)	Melanoma, typically in combination with nivolumab.

Surveillance:

Consider multidisciplinary discussion via BSMO BITOX Immunomanager submission
https://bsmo.be/multidiscplin-immunotox-meeting/

References

Patel RP, Parikh R, Gunturu KS, Tariq RZ, Dani SS, Ganatra S, Nohria A. Cardiotoxicity of Immune Checkpoint Inhibitors. Curr Oncol Rep. 2021 May 3;23(7):79. doi: 10.1007/s11912-021-01070-6. PMID: 33937956; PMCID: PMC8088903
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

TKI

Multi Kinase Inhibitors

Drug class / agents

Main oncologic indications

Type of cardiotoxicity

Approximate risk

Vascular endothelial growth factor inhibitors VEGF (VEGFi)

Sunitinib (Sutent®)

Sorafenib (Nexavar®)

Pazopanib (Votrient®)

Axitinib (Inlyta®)

Lenvatinib (Lenvima®)

Cabozantinib (Cabometyx® / Cometriq®)

Regorafenib (Stivarga®)

Vandetanib (Caprelsa®)

Renal cell carcinoma,
hepatocellular carcinoma,
differentiated and medullary thyroid cancers,
GIST,
some other rare solid tumors depending on the specific agent.

Hypertension (very common)
LV dysfunction / heart failure

Hypertension (all grades): 20–70% (Grade 3–4: 10–20%)
Heart failure: 5–15% • Symptomatic CHF up to ~10–15% (higher with specific agents, eg. Sunitinib)
QT prolongation: 5–15%

Angiogenesis inhibitor related cardiovascular toxicities

Proposed Surveillance (ESC guidelines):

NTproBNP is not reimbursed in Belgium

References

Touyz RM, Herrmann J. Cardiotoxicity with vascular endothelial growth factor inhibitor therapy. NPJ Precis Oncol. 2018 May 8;2:13. doi: 10.1038/s41698-018-0056-z. PMID: 30202791; PMCID: PMC5988734.
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

ALK Inhibitors

Drug class / agents

Main oncologic indications

Type of cardiotoxicity

Approximate risk & surveillance

ALK inhibitors Crizotinib, Ceritinib, Alectinib, Brigatinib, Lorlatinib

ALK-positive NSCLC.

ROS1-positive NSCLC (selected agents).

Other rare ALK-driven tumours.

Bradycardia (most common)
QT prolongation
Rare LV dysfunction or other arrhythmias

Bradycardia: ~10–20%, often asymptomatic.

QT prolongation: ~5–10%.

EGFR inhibitors Erlotinib, Lapatinib

EGFR-mutated NSCLC (erlotinib). HER2-positive metastatic breast cancer (lapatinib, usually with capecitabine).

QT prolongation
Rare LV dysfunction, myocardial ischemia

Overall low cardiovascular risk (<2–3%)

Surveillance :

ALK and EGFR inhibitors are non-angiogenic TKIs with a cardiovascular toxicity profile dominated by electrical disturbances rather than vascular toxicity, and generally require limited routine cardiac surveillance. Individualized approach is therefore recommended

References

Liu Y, Chen C, Rong C, He X, Chen L. Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor-Associated Cardiotoxicity: A Recent Five-Year Pharmacovigilance Study. Front Pharmacol. 2022 Mar 17;13:858279. doi: 10.3389/fphar.2022.858279. PMID: 35370632; PMCID: PMC8968911.
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

BCR-ABL Inhibitors

Drug class / agents

Main oncologic / hematologic indications

Type of cardiotoxicity

Approximate risk (agent-specific where relevant)

BCR-ABL inhibitors Imatinib (Glivec®) Dasatinib (Sprycel®) Nilotinib (Tasigna®) Ponatinib (Iclusig®) Bosutinib (Bosulif®)

Hematologic malignancies:

Chronic myeloid leukemia (CML, all phases)
Philadelphia-positive ALL
Other rare BCR-ABL–driven neoplasms

Solid tumours:

adjuvant or metastatic gastrointestinal stromal tumours (GIST)

(Imatinib)

Left ventricular dysfunction / heart failure
QT prolongation
Pulmonary hypertension (notably with dasatinib)
Arterial occlusive events and hypertension (agent-dependent)

LV dysfunction / CHF:

Imatinib: ~1–3% (higher in elderly/comorbid patients)
Dasatinib: ~3–10%; also associated with pulmonary hypertension
Nilotinib: ~2–5%; also associated with arterial occlusive events
Ponatinib: HF ~5–10%, hypertension >40–50%, high arterial thrombotic risk

QT prolongation (significant): ~5–15% (variable across agents)

BCR-ABL inhibitors related cardiovascular toxicities

Proposed Surveillance (ESC guidelines):

References

Weisfelner Bloom M et al. Cardio-Oncology and Heart Failure: a Scientific Statement From the Heart Failure Society of America. Journal of Cardiac Failure Volume 31, Issue 2 p 415-455February 2025
Sayegh et al. Cardiovascular Toxicities Associated with Tyrosine Kinase Inhibitors. Curr Cardiol Rep. 2023 April ; 25(4): 269–280. doi:10.1007/s11886-023-01845-2
Mendez-Ruiz et al. Bleeding Risk With Antiplatelets and Bruton’s Tyrosine Kinase Inhibitors in Patients With Percutaneous Coronary Intervention. Journal of the Society for Cardiovascular Angiography & Interventions, Volume 2, Issue 3, 2023. https://doi.org/10.1016/j.jscai.2023.100608.
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

BTK Inhibitors

Drug class / agents

Main hematologic indications

Type of cardiotoxicity

Approximate risk (agent-specific where relevant)

BTK inhibitors Ibrutinib (Imbruvica®) Acalabrutinib (Calquence®) Zanubrutinib (Brukinsa®)

B-cell malignancies:

Chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL)
Waldenström macroglobulinemia
Mantle cell lymphoma
Other B-cell non-Hodgkin lymphomas

Atrial fibrillation
Arterial hypertension
Heart failure (diastolic and/or systolic)
Rare ventricular arrhythmias (not QT-related)

Heart failure: Ibrutinib: ~3.7–7.7%, Acalabrutinib: ~2.1%
Atrial fibrillation: Ibrutinib: ~6–15%, lower incidence with acalabrutinib and zanubrutinib

Arterial hypertension: Ibrutinib: up to ~78%, Acalabrutinib: up to ~54%
Ventricular arrhythmias not related to QTc prolongation) uncommon, but awareness is needed

Bleeding is very common, particularly with ibrutinib (up to ~55%), due to off-target antiplatelet effects. Individualized risk–benefit assessment is required in patients needing antiplatelet or anticoagulant therapy, especially dual antiplatelet therapy.

Proposed Surveillance (ESC guidelines) :

References

Weisfelner Bloom M et al. Cardio-Oncology and Heart Failure: a Scientific Statement From the Heart Failure Society of America. Journal of Cardiac Failure Volume 31, Issue 2 p 415-455February 2025
Sayegh et al. Cardiovascular Toxicities Associated with Tyrosine Kinase Inhibitors. Curr Cardiol Rep. 2023 April ; 25(4): 269–280. doi:10.1007/s11886-023-01845-2
Mendez-Ruiz et al. Bleeding Risk With Antiplatelets and Bruton’s Tyrosine Kinase Inhibitors in Patients With Percutaneous Coronary Intervention. Journal of the Society for Cardiovascular Angiography & Interventions, Volume 2, Issue 3, 2023. https://doi.org/10.1016/j.jscai.2023.100608.
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

RAF / MEK BTK Inhibitors

Drug class / agents

Main oncologic indications

Type of cardiotoxicity

Approximate risk

BRAF inhibitors (BRAFi) Vemurafenib (Zelboraf®)
Dabrafenib (Tafinlar®)
Encorafenib (Braftovi®)

MEK inhibitors (MEKi) Trametinib (Mekinist®)
Cobimetinib (Cotellic®)
Binimetinib (Mektovi®)
Selumetinib (Koselugo®)

BRAF-mutated unresectable or metastatic melanoma.
BRAF-mutated thyroid and colorectal cancers (often in combination regimens).
Selected rare tumours with MAPK-pathway activation, e.g. histiocytic disorders, paediatric low-grade gliomas; (drug-specific).

LV dysfunction with all BRAFi/MEKi combinations)
Arterial hypertension and pulmonary hypertension
Atrial fibrillation (BRAFi alone or combined with MEKi)
Myocardial infarction (rare)
QTc prolongation (specific to vemurafenib + cobimetinib)

LV dysfunction with all BRAFi/MEKi combinations)
Arterial hypertension and pulmonary hypertension
Atrial fibrillation (BRAFi alone or combined with MEKi)
Myocardial infarction (rare)
QTc prolongation (specific to vemurafenib + cobimetinib)

RAF/MEK inhibitor related cardiovascular toxicity

Proposed Surveillance (ESC guidelines):

Consider additional TTE 4 weeks after starting the therapy in high and very high risk patients, as most CTRCD with RAF/MEKi develop early.

References

Glen C et al. Mechanistic and Clinical Overview Cardiovascular Toxicity of BRAF and MEK Inhibitors: JACC: CardioOncology State-of-the-Art Review, JACC: CardioOncology, Volume 4, Issue 1, 2022,Pages 1-18,
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

Breast Cancer TKI (PARPi, CDK4/6i)

Drug class / agents	Main oncologic indications	Type of cardiotoxicity	Approximate risk (agent-specific where relevant)
CDK4/6 inhibitors Ribociclib (Kisqali®), Palbociclib (Ibrance®), Abemaciclib (Verzenios®)	Hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer, in combination with endocrine therapy.	QT prolongation (predominantly ribociclib) Hypertension Heart failure (uncommon) Atrial fibrillation (reported in real-world data)	QT prolongation (ribociclib): QTc>480 ms ~15–20%, QTc>500 ms: ~3–5% Heart failure <2–3%. Hypertension: Palbociclib: ~10–15%, Abemaciclib: ~10–20% Atrial fibrillation <5%. VTE (abemaciclib): 2–5%.
PARP inhibitors (PARPi) Olaparib, Talazoparib	Germline BRCA1/2–mutated, HER2-negative breast cancer: High-risk early-stage (adjuvant olaparib) Metastatic disease	No consistent association with CTRCD, arrhythmias, or hypertension

In oncology patients, the Fridericia formula (QTcF = QT/RR¹ᐟ³) is preferred for QT correction because it reduces the overestimation of QT prolongation seen with Bazett’s formula — particularly at higher heart rates — and minimizes inappropriate management changes during QT-prolonging cancer therapy.

Proposed Surveillance for patients receiving CDK4/6i (ESC guidelines):

No cardiovascular surveillance is required for patients receiving PARPi

References

Park C, Liu YS, Kenawy AS, Lin YH, Liu Y, Heo JH. Cardiovascular Adverse Events and Associated Costs of CDK4/6 Inhibitors in Patients With Breast Cancer. J Natl Compr Canc Netw. 2025 Apr 18;23(5):e257001. doi: 10.6004/jnccn.2025.7001. PMID: 40250478.
Pavlovic D, Niciforovic D, Papic D, Milojevic K, Markovic M. CDK4/6 inhibitors: basics, pros, and major cons in breast cancer treatment with specific regard to cardiotoxicity – a narrative review. Ther Adv Med Oncol. 2023 Oct 11;15:17588359231205848.
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)
Palazzo A et al. Major adverse cardiac events and cardiovascular toxicity with PARP inhibitors-based therapy for solid tumors: a systematic review and safety meta-analysis. ESMO Open. 2023 Apr;8(2):101154. Eur Heart Journal (2022) 43, 4229–4361
Richardson DR et al. Association of QTc Formula With the Clinical Management of Patients With Cancer. JAMA Oncol.2022;8(11):1616–1623. doi:10.1001/jamaoncol.2022.4194

Angiogenesis inhibitors

Drug class / agents

Main oncologic indications

Type of cardiotoxicity

Approximate risk

anti-VEGF monoclonal antibodies Bevacizumab (Avastin®)

Colorectal cancer, renal cell carcinoma,
NSCLC,
ovarian and cervical cancer,
selected primary brain tumors (e.g. meningioma).

Hypertension (most common)
Left ventricular dysfunction / heart failure
Arterial thromboembolic events (myocardial infarction, stroke)

Hypertension (all grades): 20–40% (Grade 3–4: 5–15%)
Heart failure: 1–4%

Vascular endothelial growth factor inhibitors VEGF (VEGFi)

Sunitinib (Sutent®)

Sorafenib (Nexavar®)

Pazopanib (Votrient®)

Axitinib (Inlyta®)

Lenvatinib (Lenvima®)

Cabozantinib (Cabometyx® / Cometriq®)

Regorafenib (Stivarga®)

Vandetanib (Caprelsa®)

Renal cell carcinoma,
hepatocellular carcinoma,
differentiated and medullary thyroid cancers,
GIST,
some other rare solid tumors depending on the specific agent.

Hypertension (very common)
LV dysfunction / heart failure

Hypertension (all grades): 20–70% (Grade 3–4: 10–20%)
Heart failure: 5–15% • Symptomatic CHF up to ~10–15% (higher with specific agents, eg. Sunitinib)
QT prolongation: 5–15%

Angiogenesis inhibitor related cardiovascular toxicities

Proposed Surveillance (ESC guidelines) :

NTproBNP is not reimbursed in Belgium

References

Touyz RM, Herrmann J. Cardiotoxicity with vascular endothelial growth factor inhibitor therapy. NPJ Precis Oncol. 2018 May 8;2:13. doi: 10.1038/s41698-018-0056-z. PMID: 30202791; PMCID: PMC5988734.
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

Endocrine therapy women

SERM

Drug class / agents (commercial names)	Main oncologic indications	Type of cardiotoxicity	Approximate risk
Aromatase inhibitors (AIs) Anastrozole (Arimidex®) Letrozole (Femara®) Exemestane (Aromasin®)	Hormone receptor–positive, HER2-negative breast cancer (adjuvant and metastatic). Occasionally other hormone-sensitive malignancies.	Dyslipidaemia Hypertension Ischemic heart disease Increased overall cardiovascular event risk	Absolute CV risk generally small. Relative CV risk can be 10–25% higher compared with tamoxifen, especially in patients with pre-existing CV risk factors.
Selective estrogen receptor modulators (SERMs) Tamoxifen (Nolvadex®) Raloxifene (Evista®)	Hormone receptor–positive breast cancer (adjuvant and metastatic). Breast cancer risk reduction in high-risk women.	Venous thromboembolism (DVT, PE, stroke) Diabetes mellitus	Venous thromboembolism: ~1–3% per year. Risk increased with older age, obesity, immobility, and prior VTE.

Okwuosa TM et al. June 2021

Proposed Surveillance (ESC guidelines) :

References

Rana, S., et al. (2023). “The Cardiovascular Risks Associated with Aromatase Inhibitors, Tamoxifen, and GnRH Agonists in Women with Breast Cancer.” Current Atherosclerosis Reports, 25(4), 145-154.
Okwuosa TM et al. ‘Impact of Hormonal Therapies for the Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart Association’. Circulation: Genomic and Precision Medicine Vol 14 Issue 3, June 2021
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

GrRH Agonists

Drug class / agents (commercial names)

Main oncologic indications

Type of cardiotoxicity

Approximate risk & surveillance

GnRH agonists Leuprolide (Lucrin®, Eligard®) Goserelin (Zoladex®) Triptorelin (Decapeptyl®, Diphereline®)

Prostate cancer:

Localized, locally advanced, and metastatic disease
Neoadjuvant/adjuvant androgen deprivation with radiotherapy
Biochemical recurrence after primary treatment

Breast cancer:

Ovarian suppression in premenopausal HR-positive breast cancer (mainly triptorelin)

Mainly driven through indirect effects on cardiovascular risk factors:

hypertension, hyperlipidaemia, hyperglycaemia / insulin resistance, metabolic syndrome

Increased risk of ischemic heart disease, myocardial infarction, and stroke

• Slight QTc prolongation

Cardiovascular events ~6–20% (higher in patients with pre-existing CV disease)

Proposed Surveillance (ESC guidelines):

References

Rana, S., et al. (2023). “The Cardiovascular Risks Associated with Aromatase Inhibitors, Tamoxifen, and GnRH Agonists in Women with Breast Cancer.” Current Atherosclerosis Reports, 25(4), 145-154.
Okwuosa TM et al. ‘Impact of Hormonal Therapies for the Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart Association’. Circulation: Genomic and Precision Medicine Vol 14 Issue 3, June 2021
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

Endocrine therapy men

GrRH Agonists

Drug class / agents (commercial names)

Main oncologic indications

Type of cardiotoxicity

Approximate risk & surveillance

GnRH agonists Leuprolide (Lucrin®, Eligard®) Goserelin (Zoladex®) Triptorelin (Decapeptyl®, Diphereline®)

Prostate cancer:

Localized, locally advanced, and metastatic disease
Neoadjuvant/adjuvant androgen deprivation with radiotherapy
Biochemical recurrence after primary treatment

Breast cancer:

Ovarian suppression in premenopausal HR-positive breast cancer (mainly triptorelin)

Mainly driven through indirect effects on cardiovascular risk factors:

hypertension, hyperlipidaemia, hyperglycaemia / insulin resistance, metabolic syndrome

Increased risk of ischemic heart disease, myocardial infarction, and stroke

• Slight QTc prolongation

Cardiovascular events ~6–20% (higher in patients with pre-existing CV disease)

Proposed Surveillance (ESC guidelines):

References

Rana, S., et al. (2023). “The Cardiovascular Risks Associated with Aromatase Inhibitors, Tamoxifen, and GnRH Agonists in Women with Breast Cancer.” Current Atherosclerosis Reports, 25(4), 145-154.
Okwuosa TM et al. ‘Impact of Hormonal Therapies for the Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart Association’. Circulation: Genomic and Precision Medicine Vol 14 Issue 3, June 2021
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

GrRH Antagonists

Drug class / agents (commercial names)	Main oncologic indications	ESC-aligned cardiotoxicity profile	Approximate risk & surveillance
GnRH antagonists Degarelix (Firmagon®) Relugolix (Orgovyx®)	Prostate cancer requiring rapid testosterone suppression, particularly in advanced or metastatic disease.	Mainly driven through indirect effects on cardiovascular risk factors: hypertension, hyperlipidaemia, hyperglycaemia / insulin resistance. Increased risk of ischemic heart disease, stroke Slight QTc prolongation	Cardiovascular events: ~3% Generally lower than with GnRH agonists

GnRH antagonists are associated with a lower overall cardiovascular event rate compared with GnRH agonists, making them a preferred option in patients with high baseline cardiovascular risk, while still requiring structured cardiometabolic surveillance.

Proposed Surveillance (ESC guidelines):

References

Rana, S., et al. (2023). “The Cardiovascular Risks Associated with Aromatase Inhibitors, Tamoxifen, and GnRH Agonists in Women with Breast Cancer.” Current Atherosclerosis Reports, 25(4), 145-154.
Okwuosa TM et al. ‘Impact of Hormonal Therapies for the Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart Association’. Circulation: Genomic and Precision Medicine Vol 14 Issue 3, June 2021

ARTA

Drug class / agents (commercial names)	Main oncologic indications	Type of cardiotoxicity	Approximate risk
ARTA – early generation (non-steroidal anti-androgens) Bicalutamide (Casodex®) Flutamide (Eulexin®) Nilutamide (Anandron®) – only rearely in use			Increased CV event risk when combined with ADT. Any-grade CV events: up to 75% relative risk increase (RR ~1.75) when ARTA added to ADT. Severe (grade ≥3) CV events: up to 2-fold increase (RR ~2.10).
ARTA – second generation Enzalutamide (Xtandi®) Apalutamide (Erleada®) Darolutamide (Nubeqa®)	Prostate cancer: Metastatic hormone-sensitive PCa (mHSPC) Non-metastatic castration-resistant PCa (nmCRPC) Metastatic castration-resistant PCa (mCRPC)	Hypertension • Heart failure Ischemic events (MI, stroke) Dyslipidaemia, diabetes Slight QTc prolongation
Testosterone synthesis inhibitors Abiraterone acetate (Zytiga®)	Prostate cancer: • mHSPC • mCRPC (with prednisone)	Atrial fibrillation Fluid retention / oedema • Hypokalaemia (mineralocorticoid excess) Hypertension Heart failure Increased risk of ischemic events

Androgen receptor–targeted agents substantially increase cardiovascular risk when added to ADT, with both any-grade and severe CV events occurring more frequently, underscoring the importance of baseline cardiovascular risk assessment, blood pressure control, and metabolic monitoring.

Proposed Surveillance (ESC guidelines):

References

Rana, S., et al. (2023). “The Cardiovascular Risks Associated with Aromatase Inhibitors, Tamoxifen, and GnRH Agonists in Women with Breast Cancer.” Current Atherosclerosis Reports, 25(4), 145-154.
Okwuosa TM et al. ‘Impact of Hormonal Therapies for the Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart Association’. Circulation: Genomic and Precision Medicine Vol 14 Issue 3, June 2021
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

Radiation therapy

Commonly / frequently implicated therapies

Radiotherapy (RT) : currently indicated in +/- 50% of all new cancer diagnoses
Radiotherapy-related cardiovascular disease (RTRCD) : mainly after chest / mediastinal RT
- Breast cancer RT
- Hodgkins’ lymphoma RT (historically : mantle field RT)
- Oesophageal cancer RT
- Lung cancer RT
Important:
Total dose? Fraction dose?
Mean heart dose?
Cardiac-sparing techniques used?

There is no safe heart dose!

Mechanism of toxicity : RT-induced DNA damage à inflammation + replacement fibrosis
EVERY part of the cardiovascular system may be involved :

Pericardial disease	Acute RT-induced pericarditis (rare) Chronic pericarditis Constrictive pericarditis	Early Late Late
Coronary artery disease	Proximal fibrotic noncalcified stenoses Microvascular disease (capillary rarefaction)	Late Intermediate – late
Valvular heart disease	Aortic valve stenosis Mitral valve regurgation +/- proximal aortic calcification (porcelain aorta)	Late Late Late
Conduction disease	Bradycardia +/- arrhythmias	Late
Myocardial disease	Diastolic dysfunction (myocardial fibrosis)	Intermediate – late

Identical to ESC guidelines-based approach per pathology
Preventive measures to mitigate RT-induced CVD are currently unavailable : best prevention is limitation of delivered dose to heart & CV structures
Optimal CV risk factor management remains essential.
Follow up for late RTRCD depends on estimated risk (see the figures bellow for ESC recommendations)
Special situation : RT in patients with CIED (see below)

Diagnostic approach

Early RTRCD : rare with current RT techniques
Late RTRCD : very late (5-10-15+ years after RT)
Diagnostic approach : identical to ESC guidelines-based approach per suspected pathology

Therapeutic approach : oncological aspects

Since most RTRCD occurs late, oncological treatment is rarely affected by RTRCD
Exception : acute RT-induced pericardial disease (pericarditis +/- pericardial effusion)
à Hold RT if still ongoing and treat as pericarditis (colchicine + acetylsalicylic acid/NSAIDs)
à Attention to association of systemic treatments that may induce pericardial disease

Therapeutic approach : cardiovascular aspects

Identical to ESC guidelines-based approach per pathology
Preventive measures to mitigate RT-induced CVD are currently unavailable : best prevention is limitation of delivered dose to heart & CV structures
Optimal CV risk factor management remains essential.
Follow up for late RTRCD depends on estimated risk (see the figures bellow for ESC recommendations)
Special situation : RT in patients with CIED (see below)

ESC Recommendations for baseline risk assessment of patients before radiotherapy to a volume including the heart

RT in patients with CIED

Radiotherapy (RT)–induced malfunction of cardiac implantable electronic devices (CIEDs) is rare. Higher risk with:

higher cumulative radiation dose
CIED in the treatment volume
exposure to neutron radiation from high-energy photon beams (>10 MV). (therefore whenever feasible, non–neutron-producing RT techniques are preferred)

CIED behaviour within or near the RT treatment field remains unpredictable with potential RT-related CIED malfunctions:

Transient interference during irradiation, resulting in inappropriate sensing or triggering
Device reset to backup settings, usually reversible with reprogramming
Permanent device damage, which is rare and typically associated with direct irradiation

Therefore, established precautionary measures should be followed to minimize patient risk (see figures below)

Risk stratification before planned radiotherapy in patients with CIED

References

Lyon AR 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). Eur Heart J (2022) : 00, 1-133.
Wilson J, Hua CJ, Aziminia N, Manisty C. Imaging of the Acute and Chronic Cardiovascular Complications of Radiation Therapy. Circulation Cardiovasc Img (2025) : 18e017454.
Mitchell JD et al. State-of-the-art review. Cardiovascular Manifestations From Therapeutic Radiation. A Multidisciplinary Expert Consensus Statement From the International Cardio-Oncology Society. J Am Coll Cardiol CardioOnc (2021) : 3, 360-80.

Stem cell transplantation

Indications:

Hematologic malignancies such as acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML), aggressive and indolent lymphomas, multiple myeloma, and selected myeloproliferative neoplasms.
Non-malignant disorders such as severe aplastic anemia, congenital immunodeficiencies, and hemoglobinopathies (e.g. sickle-cell disease, thalassemia)

	Main cardiovascular complications	Key clinical considerations
Pre-HSCT (baseline assessment)		Assess cumulative exposure to cardiotoxic therapies (anthracyclines, chest RT) Optimize treatment of pre-existing cardiovascular disease and risk factors before conditioning
Early phase (<100 days post-HSCT)	Atrial fibrillation (most common) Heart failure (less frequent) Hypertension or hypotension Pericardial effusion Venous thromboembolism (VTE)	High-risk period due to conditioning toxicity, infections, fluid shifts, and inflammation Acute GVHD increases risk of thrombosis and inflammatory myocardial injury
Intermediate phase (3–12 months)	Persistent or new-onset heart failure Conduction abnormalities and arrhythmias Pericardial disease	Monitor patients with early complications or high risk for cardiotoxicity to detect subclinical LV dysfunction Define long-term survivorship plan
Late phase (>1 year post-HSCT)	Hypertension Diabetes mellitus Dyslipidaemia and metabolic syndrome Coronary artery disease (CAD) Heart failure Conduction disorders Recurrent pericardial effusion	Lifelong cardiovascular surveillance Aggressive management of traditional CV risk factors Chronic GVHD is associated with increased cardiometabolic risk
GVHD-related complications (all phases)	Acute GVHD: myocarditis, heart failure, arrhythmias, conduction disorders, pericardial effusion, thrombosis. Chronic GVHD: Progressive hypertension, diabetes mellitus, dyslipidaemia.	Multidisciplinary management with hematology and cardiology Consider immune-mediated mechanisms Lower threshold for cardiac imaging and specialist referral

Footnote for figure: BNP, B-type natriuretic peptide; BP, blood pressure; CPET, cardiopulmonary exercise testing; CV, cardiovascular; CVD, CV disease; CVRF, cardiovascular risk factors; ECG, electrocardiogram; GVHD, graft vs. host disease; HbA1c, glycated haemoglobin; HSCT, haematopoietic stem cell transplantation; M, months; NP, natriuretic peptides (including BNP or NT-proBNP); NT-proBNP, N-terminal pro-BNP; TTE, transthoracic echocardiography. aIncluding physical examination, BP, lipid profile, and HbA1c. bMediastinal or mantle field radiation, alkylating agents, >250 mg/m2 doxorubicin or equivalent. cTotal body irradiation, alkylating agents.

References

Tocchetti CG et al. Cardiovascular toxicities of immune therapies for cancer– a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology. Eur J of Heart Failure (2024) 26, 2055–2076
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244

Cart-T cell therapy

Therapy

Main oncologic indications

Type of cardiotoxicity

Approximate risk

CAR T-cell therapy (CAR-T)

(e.g. tisagenlecleucel, axicabtagene ciloleucel, lisocabtagene maraleucel, idecabtagene vicleucel, ciltacabtagene autoleucel):

Hematologic malignancies, depending on product:

B-cell acute lymphoblastic leukemia (B-ALL)
Diffuse large B-cell lymphoma and other aggressive B-cell lymphomas
Mantle cell lymphoma
Multiple myeloma

Hematologic malignancies, depending on product:

B-cell acute lymphoblastic leukemia (B-ALL)
Diffuse large B-cell lymphoma and other aggressive B-cell lymphomas
Mantle cell lymphoma
Multiple myeloma

LVEF or GLS decline: ~5–10%

Symptomatic HF: 2–15%

Acute coronary syndrome: 1.4–7%

Any arrhythmia: 0.8–12.2%

Atrial fibrillation: 0.4–7.6% Hypotension: up to 87% (often CRS-related)

Tumor-infiltrating lymphocytes (TIL)

Advanced or metastatic cutaneous melanoma.

Under investigation for other solid tumors.

Hypotension
Arrhythmias

Hypotension: ~2.6%
Atrial fibrillation: ~14%
Troponin elevation: ~2.3%

Cardiovascular toxicity from cellular immunotherapies is frequently acute and CRS-related, with arrhythmias and hypotension predominating. Prompt recognition and multidisciplinary management are essential.
Specific risk assessment tools are not available

Proposed surveillance (ESC guidelines):

NB: Patients treated with TIL or CAR-T have a relatively high mortality per se and might not profit from a close surveillance or discontinuation of an anti-cancer therapy

Consider multidisciplinary discussion via BSMO BITOX Immunomanager submission
https://bsmo.be/multidiscplin-immunotox-meeting/

Grading of cytokine release syndrome Cytokine Release Syndrome (CRS) – ASTCT Consensus Criteria

CRS Grade	Fever (≥38°C)	Hypotension	Hypoxia
Grade 1	Present	None	None
Grade 2	Present	Responsive to IV fluids (no vasopressors)	Requiring low-flow oxygen (≤6 L/min nasal cannula)
Grade 3	Present	Requiring one vasopressor (± vasopressin)	Requiring high-flow oxygen (>6 L/min), face mask, or non-rebreather
Grade 4	Present	Requiring multiple vasopressors (excluding vasopressin)	Requiring positive pressure ventilation (CPAP, BiPAP, or mechanical ventilation)

CRS most commonly occurs within the first week after CAR-T infusion.
Organ dysfunction (including cardiac dysfunction) is considered a consequence of CRS, not a grading criterion.
Cardiovascular complications during CRS include tachyarrhythmias, hypotension, LV dysfunction, and shock, most often correlating with CRS grade ≥2.

References

Tocchetti CG et al. Cardiovascular toxicities of immune therapies for cancer– a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology. Eur J of Heart Failure (2024) 26, 2055–2076
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244
Lee DW et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638.

Proteasome inhibitors

Agent

Main hematologic indications

Type of cardiotoxicity

Approximate risk

Bortezomib

(Velcade®)

Multiple myeloma (induction, consolidation, maintenance).

Mantle cell lymphoma;

Occasional use in other plasma-cell or lymphoproliferative disorders.

Heart failure
Arrhythmias
Hypertension

Less frequent than carfilzomib

All-grade cardiotoxicity: ~3–5%.
Heart failure <2–3%.

Carfilzomib

(Kyprolis®)

Relapsed/refractory multiple myeloma, typically in combination regimens (e.g. lenalidomide/dexamethasone and other)

Heart failure
Hypertension
Arrhythmias (especially atrial fibrillation)

Any cardiac event: ~15–20%.
Heart failure: 5–15% (and up to 20–25% in selected populations or higher-dose regimens)
Hypertension: 15–30%.
Atrial fibrillation: ~5–10%.

Multiple myeloma drug-related cardiovascular toxicities

Footnote: AF, atrial fibrillation; ATE, arterial thromboembolism; DM, diabetes mellitus; EMA, European Medicines Agency; FDA, Food and Drug Administration; HF, heart failure; HG, hyperglycaemia; HTN, hypertension; MedDRA, medical dictionary for regulatory activities; MI, myocardial infarction; PH, pulmonary hypertension; VTE, venous thromboembolism. Adverse reactions reported in multiple clinical trials or during post-marketing use are listed by system organ class (in MedDRA) and frequency. If the frequency is unknown or cannot be estimated from the available data, a blank space has been left. aIxazomib produces peripheral oedema in up to 18% of patients and hyperglycaemia in combination with lenalidomide or pomalidomide and dexamethasone.

Proposed Surveillance during therapie with proteosome inhibitors (ESC guidelines):

NTproBNP is not reimbursed in Belgium

Proposed Surveillance during multiple myeloma therapie (ESC guidelines):

NTproBNP is not reimbursed in Belgium

References

Buck B, Kellett E, Addison D, Vallakati A. Carfilzomib-induced Cardiotoxicity: An Analysis of the FDA Adverse Event Reporting System (FAERS). J Saudi Heart Assoc. 2022 Aug 31;34(3):134-141. doi: 10.37616/2212-5043.1311. PMID: 36127934; PMCID: PMC9458320.
Lyon A et al (2022) 2022 ESCGuidelines on cardio-oncology developed in collaboration with the European HematologyAssociation(EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart Journal (2022) 43, 4229–4361 https://doi.org/10.1093/eurheartj/ehac244
Xiao Y, Yin J, Wei J, Shang Z. Incidence and risk of cardiotoxicity associated with bortezomib in the treatment of cancer: a systematic review and meta-analysis. PLoS One. 2014 Jan 29;9(1):e87671. doi: 10.1371/journal.pone.0087671. PMID: 24489948; PMCID: PMC3906186.

Immunomodulatory drugs

Agent	Main hematologic indications	Type of cardiotoxicity	Approximate risk
Thalidomide Lenalidomide Pomalidomide	Multiple myeloma (across different lines of therapy). Myelodysplastic syndromes with isolated deletion (5q) (lenalidomide). Selected other hematologic conditions.	Venous and arterial thromboembolism (DVT, PE, myocardial infarction, stroke) Bradycardia (mainly thalidomide)	Venous thromboembolism: ~10–25%. Arterial events: ~1–5%. Risk higher with concomitant steroids or chemotherapy.

Surveillance:

no specific recommendation. Consider surveillance protocols for other anticancer drugs given in combination.

Toxicities per treatment type

Contact