Universität zu Köln

Seymour, J. F., Kipps, T. J., Eichhorst, B., Hillmen, P., D'Rozario, J., Assouline, S., Owen, C., Gerecitano, J., Robak, T., De la Serna, J., Jaeger, U., Cartron, G., Montillo, M., Humerickhouse, R., Punnoose, E. A., Li, Y., Boyer, M., Humphrey, K., Mobasher, M. and Kater, A. P. (2018). Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N. Engl. J. Med., 378 (12). S. 1107 - 1121. WALTHAM: MASSACHUSETTS MEDICAL SOC. ISSN 1533-4406

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Abstract

BACKGROUND Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. METHODS In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group). The trial design did not include crossover to venetoclax plus rituximab for patients in the bendamustine-rituximab group in whom progression occurred. The primary end point was investigator-assessed progression-free survival. RESULTS After a median follow-up period of 23.8 months, the rate of investigator-assessed progression-free survival was significantly higher in the venetoclax-rituximab group (32 events of progression or death in 194 patients) than in the bendamustine-rituximab group (114 events in 195 patients); the 2-year rates of progression-free survival were 84.9% and 36.3%, respectively (hazard ratio for progression or death, 0.17; 95% confidence interval [CI], 0.11 to 0.25; P<0.001 by the stratified log-rank test). The benefit was maintained across all clinical and biologic subgroups, including the subgroup of patients with chromosome 17p deletion; the 2-year rate of progression-free survival among patients with chromosome 17p deletion was 81.5% in the venetoclax-rituximab group versus 27.8% in the bendamustine-rituximab group (hazard ratio, 0.13; 95% CI, 0.05 to 0.29), and the 2-year rate among those without chromosome 17p deletion was 85.9% versus 41.0% (hazard ratio, 0.19; 95% CI, 0.12 to 0.32). The benefit of venetoclax plus rituximab over bendamustine plus rituximab was confirmed by an independent review committee assessment of progression-free survival and other secondary efficacy end points. The rate of grade 3 or 4 neutropenia was higher in the venetoclax-rituximab group than in the bendamustine-rituximab group, but the rates of grade 3 or 4 febrile neutropenia and infections or infestations were lower with venetoclax than with bendamustine. The rate of grade 3 or 4 tumor lysis syndrome in the venetoclax-rituximab group was 3.1% (6 of 194 patients). CONCLUSIONS Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progression-free survival than bendamustine plus rituximab.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Seymour, J. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kipps, T. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichhorst, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillmen, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED D'Rozario, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Assouline, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Owen, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerecitano, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Robak, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED De la Serna, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaeger, U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cartron, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Montillo, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Humerickhouse, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Punnoose, E. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boyer, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Humphrey, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mobasher, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kater, A. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-192490
DOI:	10.1056/NEJMoa1713976
Journal or Publication Title:	N. Engl. J. Med.
Volume:	378
Number:	12
Page Range:	S. 1107 - 1121
Date:	2018
Publisher:	MASSACHUSETTS MEDICAL SOC
Place of Publication:	WALTHAM
ISSN:	1533-4406
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MINIMAL RESIDUAL DISEASE; INDEPENDENT PREDICTOR; PROGRESSION-FREE; PLUS RITUXIMAB; TARGETING BCL2; TP53 MUTATION; 17P DELETION; OPEN-LABEL; SURVIVAL; TRIAL Multiple languages Medicine, General & Internal Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19249