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EHA 2024 | Managing the potential cardiotoxicity associated with BTKis: important considerations
Danielle Brander, MD, Duke University School of Medicine, Durham, NC, discusses the potential cardiotoxicities associated with BTK inhibitors (BTKis) when treating patients with chronic lymphocytic leukemia (CLL). While there is a much lower incidence of cardiotoxicity with second-generation BTKis compared to first-generation agents, it remains essential to discuss these potential side effects with patients. Dr Brander highlights that understanding individual risk by considering patients’ age and underlying structural cardiovascular abnormalities can inform these discussions. Additionally, it is beneficial for treating oncologists and cardiologists to collaborate and monitor patients throughout treatment so that cardiac toxicities and hypertension can be prevented or managed promptly if they appear. This interview took place at the 29th Congress of the European Hematology Association (EHA) in Madrid, Spain.
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Transcript
For BTK inhibitors, owning from, you know, the first-generation covalent ibrutinib to now second-generation covalent zanubrutinib and acalabrutinib, it had been recognized that there can be cardiac toxicities. Namely we think of atrial arrhythmias, atrial fibrillation, for example, can occur in patients on these treatments. It is much less incidence with the second-generation acala and zanubrutinib versus first-generation ibrutinib...
For BTK inhibitors, owning from, you know, the first-generation covalent ibrutinib to now second-generation covalent zanubrutinib and acalabrutinib, it had been recognized that there can be cardiac toxicities. Namely we think of atrial arrhythmias, atrial fibrillation, for example, can occur in patients on these treatments. It is much less incidence with the second-generation acala and zanubrutinib versus first-generation ibrutinib. We see that in clinical trials, real-world studies, and in two head-to-head studies where ibrutinib was compared to zanubrutinib, or ibrutinib to acalabrutinib, that the incidence of atrial fibrillation was less.
That being said, we know that the risk for atrial fibrillation beyond the drugs increases as patients are older. It increases for patients with known underlying structural cardiovascular abnormalities. And so I think, in addition to making patients aware that these toxicities can develop, it’s helpful to understand prior to patients starting what their individual risk may be. So if patients, for example, haven’t had an echocardiogram for a while and the patient is older or has never had one, there are patients where I will obtain that first. I think having a baseline EKG can also be helpful, and then, again, reviewing the patient’s risk beyond the drug for development of atrial arrhythmias.
There are also risks for development of hypertension. That can be patients without prior history of hypertension. That can be in patients with hypertension control that becomes uncontrolled. That certainly usually doesn’t happen overnight, usually you can tell patients are trending in their blood pressure being higher. And in those cases, in addition again, making patients aware that that can happen, I think very close working with either their primary care or their cardiologist is important, so that patients can monitor at home and be seen in follow-up so that their cardiologist or PCP can help in adjustment of medications and trying to prevent, you know, the continuous increase in blood pressure and prevent adverse events from that perspective of outcomes.
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Disclosures
AbbVie: consultant, site PI clinical trial (grant paid to institution), 3rd party writing support for abstract or manuscript ArQule/Merck: site PI clinical trial (grant paid to institution) Ascentage: site PI clinical trial (grant paid to institution); ended 10/2021 with PI transition AstraZeneca/Acerta: site PI clinical trial (grant paid to institution); ended 1/2023 BeiGene: site PI clinical trial (grant paid to institution), 3rd party writing support for abstract or manuscript Catapult: site PI clinical trial (grant paid to institution) DTRM: site PI clinical trial (grant paid to institution), ended 4/2023 Genentech: consultant, site PI clinical trial (grant paid to institution) Juno/Celgene/BMS: site PI clinical trial (grant paid to institution) MEI Pharma: site PI clinical trial (grant paid to institution) ended 11/2021 NeWave: site PI clinical trial (grant paid to institution) Novartis: site PI clinical trial (grant paid to institution) ended 9/2021 Nurix: site PI clinical trial (grant paid to institution) Pharmacyclics: consultant, site PI clinical trial (grant paid to institution), 3rd party writing support for abstract or manuscript TG Therapeutics: site PI clinical trial (grant paid to institution), 3rd party writing support for abstract or manuscript; ended 4/2023 Other memberships (when sponsored or consultant also included under sponsor above): NCCN panel member CLL/SLL and HCL (unpaid), informCLL registry steering committee (Pharmacyclics), CORE registry steering committee (AbbVie), CLL Society (expert medical council unpaid), Alliance in Clinical Trials: Leukemia committee member & Trial Champion of S1925 (unpaid).
