Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib

Casavecchia, Grazia; Galderisi, Maurizio; Novo, Giuseppina; Gravina, Matteo; Santoro, Ciro; Agricola, Eustachio; Capalbo, Silvana; Zicchino, Stefano; Cameli, Matteo; Righini, Francesca Maria; Monte, Ines; Tocchetti, Carlo G.; Brunetti, Natale Daniele; Cadeddu, Cristian; Mercuro, Giuseppe

doi:10.1007/s10741-020-09926-y

Cited by 20 publications

(22 citation statements)

References 45 publications

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“…Patients should be monitored for high blood pressure, evidence of arterial occlusive or thromboembolic events, and reduced cardiac function. 146 Ponatinib should be interrupted or stopped immediately for vascular occlusion and for new or worsening heart failure. Patients with cardiovascular risk factors should be referred to a cardiologist.…”

Section: Management Of Patients With Inadequate Response To Imatinibmentioning

confidence: 99%

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Deininger

Shah

Altman³

et al. 2020

Journal of the National Comprehensive Cancer Network

193

210

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Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

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Section: Management Of Patients With Inadequate Response To Imatinibmentioning

confidence: 99%

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Deininger

Shah

Altman³

et al. 2020

Journal of the National Comprehensive Cancer Network

193

210

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“…Having car di ol ogy pres ent as part of the CML edu ca tion ses sion at the 2017 Amer i can Society of Hematology meet ing dem on strated the need for closer alli ance, col lab o ra tion, and coman age ment. 64 Provisional guide lines have been published in reviews over the last sev eral years focused on man ag ing car dio vas cu lar adverse events in CML, [65][66][67] focused spe cif cally on ponatinib and nilotinib, [68][69][70] as well as posi tion papers suggesting CML clin i cal trial adverse event reporting should align with car dio vas cu lar med i cine def ni tions. 71 So, who?…”

Section: Assessing Comorbidity In the CML Patient Pop U La Tionmentioning

confidence: 99%

Lifelong TKI therapy: how to manage cardiovascular and other risks

Mauro

2021

Hematology

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Beginning with imatinib and now spanning 6 oral, highly active, and mostly safe agents, the development of specific targeted therapy for patients with chronic myeloid leukemia (CML) has created a new world featuring chronic maintenance chemotherapy for all treated as such, treatment-free remission, and functional cure after prolonged deep remission in a subset. As a result comes a necessary shift in focus from acute to chronic toxicity, increasing attention to patient comorbidities, and critical thinking around specific adverse events such as metabolic, cardiovascular, and cardiopulmonary effects, which vary from agent to agent. This review aims to pull together the state of the art of managing the “C” in CML—a chronic myeloproliferative neoplasm treated at present over many years with oral BCR-ABL-targeted agents in a population whose overall health can be complex and potentially affected by disease and therapy—and determine how we can better manage a highly treatable and increasingly curable cancer.

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“…Ponatinib adverse effects on the vascular system and atherosclerotic plaque formation are comparatively more recognized than the direct cardiotoxicity and recently reviewed [47][48][49][50][51][52][53], therefore, herein, we will only discuss in brief. In fact, ponatinib's approval was suspended in October 2013, primarily due to safety concerns arising from the increased incidence of serious vascular occlusive events.…”

Section: Ponatinib Adverse Vascular Effectsmentioning

confidence: 99%

“…As the ponatinib associated cardiovascular adverse effects are getting increasingly recognized, several guidelines/recommendations/expert opinions regarding the identification, prevention, and management of cardiovascular adverse events in CML patients on ponatinib are published [48,52,[91][92][93][94]. We refer the readers to these guidelines for detailed description; herein, we are only presenting a brief discussion with a particular emphasis on cardiotoxicity.…”

Section: A Cardio-oncologist View: Implications For the Patients Carementioning

confidence: 99%

Cardiotoxicity of the BCR-ABL1 tyrosine kinase inhibitors: Emphasis on ponatinib

Singh

Umbarkar

Tousif

et al. 2020

International Journal of Cardiology

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The advent of tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. However, cardiotoxicity associated with these targeted therapies puts the cancer survivors at higher risk. Ponatinib is a third-generation TKI for the treatment of CML patients having gatekeeper mutation T315I, which is resistant to the first and second generation of TKIs, namely, imatinib, nilotinib, dasatinib, and bosutinib. Multiple unbiased screening from our lab and others have identified ponatinib as most cardiotoxic FDA approved TKI among the entire FDA approved TKI family (total 50+). Indeed, ponatinib is the only treatment option for CML patients with T315I mutation. This review focusses on the cardiovascular risks and mechanism/s associated with CML TKIs with a particular focus on ponatinib cardiotoxicity. We have summarized our recent findings with transgenic zebrafish line harboring BNP luciferase activity to demonstrate the cardiotoxic potential of ponatinib. Additionally, we will review the recent discoveries reported by our and other laboratories that ponatinib primarily exerts its cardiotoxicity via an off-target effect on cardiomyocyte prosurvival signaling pathways, AKT and ERK. Finally, we will shed light on future directions for minimizing the adverse sequelae associated with CML-TKIs.

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Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib

Cited by 20 publications

References 45 publications

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Lifelong TKI therapy: how to manage cardiovascular and other risks

Cardiotoxicity of the BCR-ABL1 tyrosine kinase inhibitors: Emphasis on ponatinib

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