Venetoclax plus bendamustine-rituximab or bendamustine-obinutuzumab in chronic lymphocytic leukemia: final results of a phase Ib study (GO28440)

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 und Salles, Gilles (2021): Venetoclax plus bendamustine-rituximab or bendamustine-obinutuzumab in chronic lymphocytic leukemia: final results of a phase Ib study (GO28440). In: Haematologica, Bd. 106, Nr. 11: S. 2834-2844

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0390-6078
• Sprache: Englisch