• 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 Pickens, Nirav 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, and Chadi Nabhan.
• CLL Program, Leukemia Service, Division of Hematologic Oncology, Department of Internal Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA matoa@mskcc.org.
• Haematologica. 2018 Sep 1; 103 (9): 1511-1517.

AbstractVenetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective 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.Copyright© 2018 Ferrata Storti Foundation.

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