Jacqueline C. Barrientos, MD, MS
Invited discussant Jacqueline C. Barrientos, MD, MS, of Northwell Health Cancer Institute, Zucker School of Medicine at Hofstra/Northwell in Great Neck, New York, noted that, although both ibrutinib and venetoclax have shown superior results to chemotherapy, each drug is associated with toxicity.
“Ibrutinib is associated with cardiovascular toxicity and bleeding effects. Venetoclax can cause neutropenia and tumor-lysis syndrome. These adverse events can lead to treatment discontinuations,” she added.
“Ibrutinib is the only drug to demonstrate superior overall survival in CLL. In this relatively young cohort that included high-risk patients, more than 90% completed therapy, and 89% had a durable complete response of at least 1 year. The peripheral blood and bone marrow were cleared of leukemia cells in more than three-quarters of patients. The fixed-dose combination achieved high rates of progression-free survival and an overall survival rate of 98% at 24 months for all treated patients. The safety profile was favorable, with three cycles of ibrutinib leading to tumor debulking,” she said.
Dr. Barrientos said that 33 patients (21%) needed dose reductions due to adverse events. Eight patients were treated with ibrutinib and six responded, with the other two patients pending evaluation for response.
“This study underscores that an all-oral, fixed-duration combination regimen of ibrutinib and venetoclax can deliver high rates of progression-free survival at 2 years while enabling treatment-free remission for patients. This combination provides the possibility to obtain deeper responses upfront, especially in younger patients or patients with high-risk disease. This strategy can help prevent development of intolerance, disease progression, or resistance,” Dr. Barrientos stated.
DISCLOSURE: Dr. Barrientos has received honoraria from Janssen; has served as a consultant or advisor to AbbVie, AstraZeneca, BeiGene, Genentech, Gilead Sciences, Innate Pharma, and Pharmacyclics; and has received institutional research funding from AstraZeneca, Oncternal Therapeutics, and Pharmacyclics.
