Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice
| Autor: | Laurie K Pearson, Charlene C. Kabel, Paul M. Barr, Bruce D. Cheson, Chaitra S. Ujjani, Danielle M. Brander, Anthony R. Mato, Ryan Jacobs, Joanna Rhodes, Allison M. Winter, Amy A Kirkwood, Nicole Lamanna, Brian T. Hill, Alan P Skarbnik, Frederick Lansigan, John M. Pagel, Maryam Sarraf Yazdy, AnnaLynn M. Williams, Anna Schuh, Andre Goy, Hande H. Tuncer, Stephen J. Schuster, Christopher P. Fox, Colleen Dorsey, Sivraj Muralikrishnan, Mazyar Shadman, Toby A. Eyre, Arun K Singavi, John N. Allan, Nirav N. Shah, Catherine C. Coombs, Hannah Morse, Neil Bailey, Andrea Sitlinger, Chadi Nabhan, Lindsey E. Roeker |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions Antineoplastic Agents Neutropenia Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Humans Dosing Practice Patterns Physicians' Adverse effect Aged Retrospective Studies Aged 80 and over Sulfonamides Dose-Response Relationship Drug business.industry Venetoclax Retrospective cohort study Middle Aged Bridged Bicyclo Compounds Heterocyclic medicine.disease Leukemia Lymphocytic Chronic B-Cell Clinical trial Tumor lysis syndrome Treatment Outcome Proto-Oncogene Proteins c-bcl-2 Oncology chemistry 030220 oncology & carcinogenesis Female Patient Safety Tumor Lysis Syndrome IGHV@ business 030215 immunology |
| Zdroj: | Clin Cancer Res |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-19-0361 |
| Popis: | Purpose: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice. Experimental Design: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected. Results: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose. Conclusions: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety. |
| Databáze: | OpenAIRE |
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