Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia
- Author(s)
- Davids, MS; Hallek, M; Wierda, W; Roberts, AW; Stilgenbauer, S; Jones, JA; Gerecitano, JF; Kim, SY; Potluri, J; Busman, T; Best, A; Verdugo, ME; Cerri, E; Desai, M; Hillmen, P; Seymour, JF;
- 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
- Publisher's Version
- https://doi.org/10.1158/1078-0432.CCR-17-3761
- 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