Universität zu Köln

Stilgenbauer, Stephan, Morschhauser, Franck, Wendtner, Clemens-Martin, Cartron, Guillaume, Hallek, Michael, Eichhorst, Barbara, Kozloff, Mark F., Giever, Thomas, Lozanski, Gerard, Jiang, Yanwen, Huang, Huang, Pignataro, Daniela Soriano, Schary, William, Humphrey, Kathryn, Mobasher, Mehrdad and Salles, Gilles (2021). Venetoclax plus bendamustine-rituximab or bendamustine-obinutuzumab in chronic lymphocytic leukemia: final results of a phase Ib study (GO28440). Haematologica, 106 (11). S. 2834 - 2845. PAVIA: FERRATA STORTI FOUNDATION. ISSN 0390-6078

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Abstract

Venetoclax (Ven), an orally administered, potent BCL-2 inhibitor, has demonstrated efficacy in chronic lymphocytic leukemia (CLL) in combination with rituximab (R) or obinutuzumab (G). Our aim was to investigate the addition of bendamustine (B) to these Ven-containing regimens in relapsed/refractory (R/R) or first-line (1L) CLL. This multi-arm, non-randomized, open-label, phase Ib study was designed to evaluate the maximum tolerated dose (MTD) and safety/tolerability of Ven with BR/BG, with 3+3 dose-escalation followed by safety expansion. Patients received Ven (schedule A) or BR/BG first (schedule B) to compare safety and determine dose/schedule for expansion. Six Ven-BR/-BG cycles were to be administered, then Ven monotherapy until disease progression (R/R) or fixed-duration 1-year treatment (1L). Overall, 33 R/R and 50 1L patients were enrolled. No dose-limiting toxicities were observed (doses 100-400 mg), and the MTD was not reached. Safety was similar between schedules; no tumor lysis syndrome occurred during dose-finding. Schedule B and Ven 400 mg were chosen for expansion. The most frequent grade 3-4 toxicity was neutropenia: R/R 64%, 1L Ven-BR 85%, 1L Ven-BG 55%. Grade 3-4 infection rate was: R/R 27%, 1L Ven-BR 0%, 1L Ven-BG 27%. During expansion, one clinical and two laboratory tumor lysis syndrome cases occurred. Fewer than half the patients completed six combination therapy cycles with all study drugs; rates of bendamustine discontinuation were high. Overall response rate was 91% in R/R and 100% in 1L patients (16 of 49 1L patients received Ven for >1 year). In conclusion, addition of bendamustine to Ven-R/-G increased toxicity without apparent efficacy benefit.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Stilgenbauer, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Morschhauser, Franck UNSPECIFIED UNSPECIFIED UNSPECIFIED Wendtner, Clemens-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Cartron, Guillaume UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichhorst, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Kozloff, Mark F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Giever, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Lozanski, Gerard UNSPECIFIED UNSPECIFIED UNSPECIFIED Jiang, Yanwen UNSPECIFIED UNSPECIFIED UNSPECIFIED Huang, Huang UNSPECIFIED UNSPECIFIED UNSPECIFIED Pignataro, Daniela Soriano UNSPECIFIED UNSPECIFIED UNSPECIFIED Schary, William UNSPECIFIED UNSPECIFIED UNSPECIFIED Humphrey, Kathryn UNSPECIFIED UNSPECIFIED UNSPECIFIED Mobasher, Mehrdad UNSPECIFIED UNSPECIFIED UNSPECIFIED Salles, Gilles UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-602642
DOI:	10.3324/haematol.2020.261107
Journal or Publication Title:	Haematologica
Volume:	106
Number:	11
Page Range:	S. 2834 - 2845
Date:	2021
Publisher:	FERRATA STORTI FOUNDATION
Place of Publication:	PAVIA
ISSN:	0390-6078
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language OPEN-LABEL; CLL; IDELALISIB; CHLORAMBUCIL; COMBINATION; INHIBITOR Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60264