Haematologica (Sep 2018)
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. 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,
- Chadi Nabhan
Affiliations
- Anthony R. Mato
- CLL Program, Leukemia Service, Division of Hematologic Oncology, Department of Internal Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Meghan Thompson
- Center for CLL, Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA
- John N. Allan
- New York Presbyterian & Weill Cornell, NY, USA
- Danielle M. Brander
- Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA
- John M. Pagel
- Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer Institute, Seattle, WA, USA
- Chaitra S. Ujjani
- Georgetown University Hospital Lombardi Comprehensive Cancer Center, Washington, DC, USA
- Brian T. Hill
- Taussig Cancer Institute, Cleveland Clinic Foundation, OH, USA
- Nicole Lamanna
- Columbia University Medical Center, New York, NY, USA
- Frederick Lansigan
- Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
- Ryan Jacobs
- Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC, USA
- Mazyar Shadman
- University of Washington/Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, WA, USA
- Alan P. Skarbnik
- John Theurer Cancer Center, Hackensack Meridian Health, NJ, USA
- Jeffrey J. Pu
- Penn State Health, Hershey, PA, USA
- Paul M. Barr
- Wilmot Cancer Institute Division of Hematology/Oncology, University of Rochester Medical Center, NY, USA
- Alison R. Sehgal
- University of Pittsburgh Medical Center, PA, USA
- Bruce D. Cheson
- Georgetown University Hospital Lombardi Comprehensive Cancer Center, Washington, DC, USA
- Clive S. Zent
- Wilmot Cancer Institute Division of Hematology/Oncology, University of Rochester Medical Center, NY, USA
- Hande H. Tuncer
- Tufts Medical Center, Boston, MA, USA
- Stephen J. Schuster
- Center for CLL, Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA
- Peter V. Pickens
- Abington Hem. Onc. Assoc., Inc., Willow Grove, PA, USA
- Nirav N. Shah
- Division of Hematology & Oncology, Medical College of Wisconsin, Brookfield, WI, USA
- Andre Goy
- John Theurer Cancer Center, Hackensack Meridian Health, NJ, USA
- Allison M. Winter
- Taussig Cancer Institute, Cleveland Clinic Foundation, OH, USA
- Christine Garcia
- University of Pittsburgh Medical Center, PA, USA
- Kaitlin Kennard
- Center for CLL, Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA
- Krista Isaac
- Internal Medicine, Lankenau Medical Center, Wynnewood, PA, USA
- Colleen Dorsey
- Center for CLL, Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA
- Lisa M. Gashonia
- Center for CLL, Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA
- Arun K. Singavi
- Division of Hematology & Oncology, Medical College of Wisconsin, Brookfield, WI, USA
- Lindsey E. Roeker
- CLL Program, Leukemia Service, Division of Hematologic Oncology, Department of Internal Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Andrew Zelenetz
- CLL Program, Leukemia Service, Division of Hematologic Oncology, Department of Internal Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Annalynn Williams
- Wilmot Cancer Institute Division of Hematology/Oncology, University of Rochester Medical Center, NY, USA
- Christina Howlett
- John Theurer Cancer Center, Hackensack Meridian Health, NJ, USA
- Hanna Weissbrot
- Columbia University Medical Center, New York, NY, USA
- Naveed Ali
- Abington Hem. Onc. Assoc., Inc., Willow Grove, PA, USA
- Sirin Khajavian
- University of Washington/Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, WA, USA
- Andrea Sitlinger
- Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA
- Eve Tranchito
- Taussig Cancer Institute, Cleveland Clinic Foundation, OH, USA
- Joanna Rhodes
- Center for CLL, Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA
- Joshua Felsenfeld
- New York Presbyterian & Weill Cornell, NY, USA
- Neil Bailey
- Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer Institute, Seattle, WA, USA
- Bhavisha Patel
- Washington Hospital Center, DC, USA
- Timothy F. Burns
- Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
- Melissa Yacur
- Penn State Health, Hershey, PA, USA
- Mansi Malhotra
- Tufts Medical Center, Boston, MA, USA
- Jakub Svoboda
- Center for CLL, Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA
- Richard R. Furman
- New York Presbyterian & Weill Cornell, NY, USA
- Chadi Nabhan
- Cardinal Health, Dublin, OH, USA
- DOI
- https://doi.org/10.3324/haematol.2018.193615
- Journal volume & issue
-
Vol. 103,
no. 9
Abstract
Venetoclax 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.
