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Updated: May 12, 2026
Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique
Published on: November 11, 2022
Electrocardiographic studies of romidepsin demonstrate its safety and identify a potential role for K(ATP) channel
Anne M Noonan1, Robin A Eisch, David J Liewehr
1Medical Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Purpose:
Romidepsin is a histone deacetylase inhibitor (HDI) approved for the treatment of both cutaneous and peripheral T-cell lymphoma (CTCL and PTCL). During development, a thorough assessment of cardiac toxicity was conducted.
Experimental Design:
A phase II single-agent nonrandomized study of romidepsin was conducted in patients with CTCL or PTCL who had progressed after at least 1 prior systemic therapy.
Results:
Results for the first 42 patients enrolled on the NCI 1312 phase II study of romidepsin in CTCL or PTCL showed no cardiac toxicity based on serial electrocardiograms (ECG), troponins, and MUGA scans/echocardiograms. The cardiac assessments reported herein confirm the safety of romidepsin among 131 enrolled patients, while supporting a role for electrolyte replacement. Heart rate increased an average 11 bpm following romidepsin infusion; there was no evidence of increased arrhythmia. Criteria for potassium/magnesium replacement were met before 55% of 1365 romidepsin doses; an association with hypoalbuminemia was confirmed. We propose a mechanism for ST segment flattening and depression, the most common ECG abnormalities observed: HDI-induced alteration of the activity or expression of KATP channels. In addition, examination of the variants of the active transporter of romidepsin, ABCB1, showed a trend toward smaller heart rate changes in the peri-infusion period among wild-type than variant diplotypes.
Conclusions:
We conclude that in the context of appropriate attention to electrolyte levels, the data support the cardiac safety of romidepsin.
Insights
Romidepsin, a treatment for T-cell lymphoma, showed no significant cardiac toxicity in a phase II study. Careful electrolyte management is key to its cardiac safety in patients receiving this histone deacetylase inhibitor.
Area of Science:
- Oncology
- Pharmacology
- Cardiology
Background:
- Romidepsin is an approved histone deacetylase inhibitor (HDI) for T-cell lymphomas.
- Cardiac safety assessments are crucial for HDI therapies like romidepsin.
Purpose of the Study:
- To evaluate the cardiac toxicity of romidepsin in patients with cutaneous T-cell lymphoma (CTCL) or peripheral T-cell lymphoma (PTCL).
Main Methods:
- A phase II, single-agent, nonrandomized study enrolled patients with CTCL or PTCL who had prior systemic therapy.
- Cardiac safety was assessed using serial electrocardiograms (ECG), troponins, and MUGA scans/echocardiograms in 131 patients.
Main Results:
- No significant cardiac toxicity was observed in 131 patients treated with romidepsin.
- An average heart rate increase of 11 bpm occurred post-infusion without increased arrhythmia.
- Electrolyte replacement criteria were met for 55% of doses, associated with hypoalbuminemia; ST segment changes were linked to KATP channel activity.
Conclusions:
- Romidepsin demonstrates cardiac safety in patients with T-cell lymphomas when electrolyte levels are appropriately managed.
- Understanding HDI effects on KATP channels may explain ECG abnormalities.
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