Universität zu Köln

Davids, Matthew S., Hallek, Michael, Wierda, William, Roberts, Andrew W., Stilgenbauer, Stephan, Jones, Jeffrey A., Gerecitano, John F., Kim, Su Young, Potluri, Jalaja, Busman, Todd, Best, Andrea, Verdugo, Maria E., Cerri, Elisa, Desai, Monali, Hillmen, Peter and Seymour, John F. (2018). Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia. Clin. Cancer Res., 24 (18). S. 4371 - 4380. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3265

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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. Patients and Methods: We conducted a comprehensive analysis of the safety of 400 mg 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 (AE) 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 400 mg. 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. (C) 2018 AACR.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Davids, Matthew S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Wierda, William UNSPECIFIED UNSPECIFIED UNSPECIFIED Roberts, Andrew W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stilgenbauer, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Jones, Jeffrey A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerecitano, John F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kim, Su Young UNSPECIFIED UNSPECIFIED UNSPECIFIED Potluri, Jalaja UNSPECIFIED UNSPECIFIED UNSPECIFIED Busman, Todd UNSPECIFIED UNSPECIFIED UNSPECIFIED Best, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Verdugo, Maria E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cerri, Elisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Desai, Monali UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillmen, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Seymour, John F. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-172869
DOI:	10.1158/1078-0432.CCR-17-3761
Journal or Publication Title:	Clin. Cancer Res.
Volume:	24
Number:	18
Page Range:	S. 4371 - 4380
Date:	2018
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	1557-3265
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TUMOR LYSIS SYNDROME; PHASE-I; INHIBITOR; BCL2; LYMPHOMA Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17286