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:
CreatorsEmailORCIDORCID Put Code
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morschhauser, FranckUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wendtner, Clemens-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cartron, GuillaumeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eichhorst, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kozloff, Mark F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giever, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lozanski, GerardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jiang, YanwenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huang, HuangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pignataro, Daniela SorianoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schary, WilliamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Humphrey, KathrynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mobasher, MehrdadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salles, GillesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
OPEN-LABEL; CLL; IDELALISIB; CHLORAMBUCIL; COMBINATION; INHIBITORMultiple languages
HematologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60264

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