Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia
Details
Publication Year 2018-09,Volume 24,Issue #18,Page 4371-4379
Journal Title
Clinical Cancer Research
Publication Type
Journal Article
Abstract
PURPOSE: The oral BCL-2 inhibitor venetoclax is an effective therapy for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including disease with high-risk genomic features such as chromosome 17p deletion (del[17p]) or progressive disease following B-cell receptor pathway inhibitors. EXPERIMENTAL DESIGN: We conducted a comprehensive analysis of the safety of 400mg daily venetoclax monotherapy in 350 patients with CLL using an integrated dataset from three phase-I/II studies. RESULTS: Median age was 66 years and 60% had del(17p). Patients had received a median of three prior therapies (range: 0-15); 42% previously received ibrutinib or idelalisib. Median duration of exposure to venetoclax was 16 months (0-56). In the pooled analysis, the most common adverse events (AEs) of any grade were diarrhea (41%), neutropenia (40%), nausea (39%), anemia (31%), fatigue (28%), and upper respiratory tract infection (25%). The most common grade 3/4 AEs were neutropenia (37%), anemia (17%), and thrombocytopenia (14%). With the current 5-week ramp-up dosing, the incidence of laboratory TLS was 1.4% (2/166), none had clinical sequelae, and all of these patients were able to ramp-up to a daily dose of 400mg. Grade 3/4 neutropenia was manageable with growth-factor support and dose adjustments; the incidence of serious infections in these patients was 15%. Ten percent of patients discontinued venetoclax due to AEs and 8% died while on study, with the majority of deaths in the setting of disease progression. CONCLUSIONS: Venetoclax as a long-term continuous therapy is generally well-tolerated in patients with R/R CLL when initiated with the current treatment algorithm.
Publisher
AACR
Research Division(s)
Cancer And Haematology
PubMed ID
29895707
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2018-06-27 09:13:24
Last Modified: 2018-10-22 11:13:40
An error has occurred. This application may no longer respond until reloaded. Reload 🗙