Venetoclax plus bendamustine-rituximab or ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Venetoclax plus bendamustine-rituximab or bendamustine-obinutuzumab in chronic lymphocytic leukemia: final results of a phase 1b study (GO28440)
Auteur(s) :
Stilgenbauer, Stephan [Auteur]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Wendtner, Clemens-Martin [Auteur]
Cartron, Guillaume [Auteur]
Hallek, Michael [Auteur]
Eichhorst, Barbara [Auteur]
Kozloff, Mark F. [Auteur]
Giever, Thomas [Auteur]
Lozanski, Gerard [Auteur]
Jiang, Yanwen [Auteur]
Huang, Huang [Auteur]
Pignataro, Daniela Soriano [Auteur]
Schary, William [Auteur]
Humphrey, Kathryn [Auteur]
Mobasher, Mehrdad [Auteur]
Salles, Gilles [Auteur]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Wendtner, Clemens-Martin [Auteur]
Cartron, Guillaume [Auteur]
Hallek, Michael [Auteur]
Eichhorst, Barbara [Auteur]
Kozloff, Mark F. [Auteur]
Giever, Thomas [Auteur]
Lozanski, Gerard [Auteur]
Jiang, Yanwen [Auteur]
Huang, Huang [Auteur]
Pignataro, Daniela Soriano [Auteur]
Schary, William [Auteur]
Humphrey, Kathryn [Auteur]
Mobasher, Mehrdad [Auteur]
Salles, Gilles [Auteur]
Titre de la revue :
Haematologica
Numéro :
106
Pagination :
2834-2844
Éditeur :
Ferrata Storti Foundation
Date de publication :
2020-11-11
ISSN :
1592-8721
Mot(s)-clé(s) en anglais :
Antibodies
Monoclonal
Humanized
Antineoplastic Combined Chemotherapy Protocols
Bendamustine Hydrochloride
Bridged Bicyclo Compounds
Heterocyclic
Humans
Leukemia
Lymphocytic
Chronic
B-Cell
Rituximab
Sulfonamides
Monoclonal
Humanized
Antineoplastic Combined Chemotherapy Protocols
Bendamustine Hydrochloride
Bridged Bicyclo Compounds
Heterocyclic
Humans
Leukemia
Lymphocytic
Chronic
B-Cell
Rituximab
Sulfonamides
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hématologie
Sciences du Vivant [q-bio]/Cancer
Sciences du Vivant [q-bio]/Sciences pharmaceutiques/Pharmacologie
Sciences du Vivant [q-bio]/Immunologie/Immunothérapie
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hématologie
Sciences du Vivant [q-bio]/Cancer
Sciences du Vivant [q-bio]/Sciences pharmaceutiques/Pharmacologie
Sciences du Vivant [q-bio]/Immunologie/Immunothérapie
Résumé en anglais : [en]
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 ...
Lire la suite >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, nonrandomized, 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 (clinicaltrial gov. Identifier: NCT01671904).Lire moins >
Lire la suite >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, nonrandomized, 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 (clinicaltrial gov. Identifier: NCT01671904).Lire moins >
Langue :
Anglais
Comité de lecture :
Oui
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Équipe(s) de recherche :
Modélisation biopharmaceutique et pharmacocinétique
Date de dépôt :
2023-05-25T03:25:22Z
2023-09-22T13:56:57Z
2023-09-22T13:56:57Z
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