Universität zu Köln

Roberts, Andrew W., Ma, Shuo, Kipps, Thomas J., Coutre, Steven E., Davids, Matthew S., Eichhorst, Barbara, Hallek, Michael, Byrd, John C., Humphrey, Kathryn, Zhou, Lang, Chyla, Brenda, Nielsen, Jacqueline, Potluri, Jalaja, Kim, Su Young, Verdugo, Maria, Stilgenbauer, Stephan, Wierda, William G. and Seymour, John F. (2019). Efficacy of venetoclax in relapsed chronic lymphocytic leukemia is influenced by disease and response variables. Blood, 134 (2). S. 111 - 123. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

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Abstract

To define the efficacy of venetoclax with extended follow-up and identify clinical or biological treatment effect modifiers, updated data for previously treated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) enrolled in 4 early-phase trials were pooled. Rates of response, complete remission (CR/CRi), and undetectable minimal residual disease (U-MRD) were analyzed for all patients (n = 436) and for those patients who were planned to receive 400 mg/day monotherapy (n = 347). Univariate and multiple regression analyses were performed to identify the pretreatment factors associated with response rates and duration of response (DoR). Objective responses were documented in 75% of all patients, including 22% CR/CRi. Overall, 27% and 16% of the patients achieved U-MRD in blood and marrow, respectively. Estimated median progression-free survival (PFS), DoR, and time to progression were 30.2, 38.4, and 36.9 months, respectively. Similar efficacy outcomes were observed within the 400 mg/day monotherapy subset. For those who achieved CR/CRi, the 3-year PFS estimate was 83%. DoR was superior for patients achieving CR/CRi or U-MRD in landmark analyses. In multiple regression analyses, bulky lymphadenopathy (>= 5 cm) and refractoriness to B-cell receptor inhibitor (BCRi) therapy were significantly associated with lower CR rate and shorter DoR. Fewer prior therapies were associated with higher CR rate, but not DoR. Chromosome 17p deletion and/or TP53 mutation and NOTCH1 mutation were consistently associated with shorter DoR, but not probability of response. Thus, both pretreatment factors and depth of response correlated with DoR with venetoclax. Patients without bulky lymphadenopathy, BCRi-refractory CLL, or an adverse mutation profile had the most durable benefit.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Roberts, Andrew W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ma, Shuo UNSPECIFIED UNSPECIFIED UNSPECIFIED Kipps, Thomas J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Coutre, Steven E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Davids, Matthew S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichhorst, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Byrd, John C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Humphrey, Kathryn UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhou, Lang UNSPECIFIED UNSPECIFIED UNSPECIFIED Chyla, Brenda UNSPECIFIED UNSPECIFIED UNSPECIFIED Nielsen, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Potluri, Jalaja UNSPECIFIED UNSPECIFIED UNSPECIFIED Kim, Su Young UNSPECIFIED UNSPECIFIED UNSPECIFIED Verdugo, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Stilgenbauer, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wierda, William G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Seymour, John F. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-135218
DOI:	10.1182/blood.2018882555
Journal or Publication Title:	Blood
Volume:	134
Number:	2
Page Range:	S. 111 - 123
Date:	2019
Publisher:	AMER SOC HEMATOLOGY
Place of Publication:	WASHINGTON
ISSN:	1528-0020
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INHIBITOR; BCL2; RITUXIMAB; CLL Multiple languages Hematology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13521