Real-world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States

Anthony R. Mato, Meghan Thompson, John N. Allan, Danielle M. Brander, John M. Pagel, Chaitra S. Ujjani, Brian T. Hill, Nicole Lamanna, Frederick Lansigan, Ryan Jacobs, Mazyar Shadman, Alan P. Skarbnik, Jeffrey J. Pu, Paul M. Barr, Alison R. Sehgal, Bruce D. Cheson, Clive S. Zent, Hande H. Tuncer, Stephen J. Schuster, Peter V. PickensNirav N. Shah, Andre Goy, Allison M. Winter, Christine Garcia, Kaitlin Kennard, Krista Isaac, Colleen Dorsey, Lisa M. Gashonia, Arun K. Singavi, Lindsey E. Roeker, Andrew Zelenetz, Annalynn Williams, Christina Howlett, Hanna Weissbrot, Naveed Ali, Sirin Khajavian, Andrea Sitlinger, Eve Tranchito, Joanna Rhodes, Joshua Felsenfeld, Neil Bailey, Bhavisha Patel, Timothy F. Burns, Melissa Yacur, Mansi Malhotra, Jakub Svoboda, Richard R. Furman, Chadi Nabhan

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Venetoclax is a BCL2 in hibi to r approve d for 17p-delet ed relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retro-spective cohort analysis of patients with chronic lymphocytic leukemia treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26.8% complex karyotype (≥ 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients, the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study.

Original languageEnglish (US)
Pages (from-to)1511-1517
Number of pages7
JournalHaematologica
Volume103
Issue number9
DOIs
StatePublished - Aug 31 2018
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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