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      A Rare Case of Severe Hypokalemia and Hypomagnesemia due to Venetoclax and Polypharmacy Leading to Life-Threatening Cardiac Arrhythmias

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          Abstract

          Venetoclax is a novel agent used in hematologic malignancies. Although no long-term studies have directly implicated venetoclax, few studies show possible association with electrolyte abnormalities. Severe derangements in serum electrolyte levels can cause cardiac dysrhythmias, which can be potentially fatal. We present a case of venetoclax in association with the other medications causing life-threatening arrhythmias. Hypothesized mechanisms include damage to the distal tubules causing loss of potassium and magnesium. Our patient required modification of his medications and aggressive repletion of electrolytes with good outcomes. For patients on venetoclax, especially those with polypharmacy, caution should be exercised to prevent severe electrolyte derangements, which can lead to life-threatening arrhythmias.

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          Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

          Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts. Treatment commenced with a 3-week dose ramp-up period for most patients in dose-escalation cohorts and for all patients in safety expansion. Results NHL subtypes included mantle cell lymphoma (MCL; n = 28), follicular lymphoma (FL; n = 29), diffuse large B-cell lymphoma (DLBCL; n = 34), DLBCL arising from chronic lymphocytic leukemia (Richter transformation; n = 7), Waldenström macroglobulinemia (n = 4), and marginal zone lymphoma (n = 3). Venetoclax was generally well tolerated. Clinical tumor lysis syndrome was not observed, whereas laboratory tumor lysis syndrome was documented in three patients. Treatment-emergent adverse events were reported in 103 patients (97%), a majority of which were grade 1 to 2 in severity. Grade 3 to 4 events were reported in 59 patients (56%), and the most common were hematologic, including anemia (15%), neutropenia (11%), and thrombocytopenia (9%). Overall response rate was 44% (MCL, 75%; FL, 38%; DLBCL, 18%). Estimated median progression-free survival was 6 months (MCL, 14 months; FL, 11 months; DLBCL, 1 month). Conclusion Selective targeting of BCL-2 with venetoclax was well tolerated, and single-agent activity varied among NHL subtypes. We determined 1,200 mg to be the recommended single-agent dose for future studies in FL and DLBCL, with 800 mg being sufficient to consistently achieve durable response in MCL. Additional investigations including combination therapy to augment response rates and durability are ongoing.
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            Management of Venetoclax-Posaconazole Interaction in Acute Myeloid Leukemia Patients: Evaluation of Dose Adjustments.

            The effect of posaconazole, a strong cytochrome P450 3A (CYP3A) inhibitor and commonly used antifungal agent, on the pharmacokinetic properties of venetoclax, a CYP3A substrate, was evaluated in patients with acute myeloid leukemia to determine the dose adjustments needed to manage this potential interaction.
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              Mechanisms, Risk Factors, and Management of Acquired Long QT Syndrome: A Comprehensive Review

              Long QT syndrome is characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram and is associated with precipitation of torsade de pointes (TdP), a polymorphic ventricular tachycardia that may cause sudden death. Acquired long QT syndrome describes pathologic excessive prolongation of the QT interval, upon exposure to an environmental stressor, with reversion back to normal following removal of the stressor. The most common environmental stressor in acquired long QT syndrome is drug therapy. Acquired long QT syndrome is an important issue for clinicians and a significant public health problem concerning the large number of drugs with this adverse effect with a potentially fatal outcome, the large number of patients exposed to these drugs, and our inability to predict the risk for a given individual. In this paper, we focus on mechanisms underlying QT prolongation, risk factors for torsades de pointes and describe the short- and long-term treatment of acquired long QT syndrome.
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                Author and article information

                Journal
                Case Rep Oncol
                Case Rep Oncol
                CRO
                CRO
                Case Reports in Oncology
                S. Karger AG (Basel, Switzerland )
                1662-6575
                14 November 2023
                Jan-Dec 2023
                14 November 2023
                : 16
                : 1
                : 1390-1394
                Affiliations
                [1]Department of Internal Medicine, Hackensack Meridian Health, Palisades Medical Center, North Bergen, NJ, USA
                Author notes
                Correspondence to: Sai Priyanka Pulipaka, sppulipaka@ 123456gmail.com
                Article
                534135
                10.1159/000534135
                10645436
                9aaddc9c-fbd6-430b-a28e-4cbdad76734e
                © 2023 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 6 January 2023
                : 8 September 2023
                : 2023
                Page count
                Figures: 2, Tables: 1, References: 8, Pages: 5
                Funding
                No funding was received for this research.
                Categories
                Case Report

                Oncology & Radiotherapy
                venetoclax,hypokalemia,arrhythmia,torsades
                Oncology & Radiotherapy
                venetoclax, hypokalemia, arrhythmia, torsades

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