Gemtuzumab ozogamicin in NPM1-mutated acute myeloid leukemia

• Verfasst von: Schlenk, Richard Friedrich [VerfasserIn]
• Verfasst von: Paschka, Peter [VerfasserIn]
• Verfasst von: Krzykalla, Julia [VerfasserIn]
• Verfasst von: Weber, Daniela [VerfasserIn]
• Verfasst von: Kapp-Schwoerer, Silke [VerfasserIn]
• Verfasst von: Gaidzik, Verena I. [VerfasserIn]
• Verfasst von: Leis, Claudia [VerfasserIn]
• Verfasst von: Fiedler, Walter [VerfasserIn]
• Verfasst von: Kindler, Thomas [VerfasserIn]
• Verfasst von: Schroeder, Thomas [VerfasserIn]
• Verfasst von: Mayer, Karin [VerfasserIn]
• Verfasst von: Lübbert, Michael [VerfasserIn]
• Verfasst von: Wattad, Mohammed [VerfasserIn]
• Verfasst von: Götze, Katharina [VerfasserIn]
• Verfasst von: Horst, Heinz A. [VerfasserIn]
• Verfasst von: Koller, Elisabeth [VerfasserIn]
• Verfasst von: Wulf, Gerald [VerfasserIn]
• Verfasst von: Schleicher, Jan [VerfasserIn]
• Verfasst von: Bentz, Martin [VerfasserIn]
• Verfasst von: Greil, Richard [VerfasserIn]
• Verfasst von: Hertenstein, Bernd [VerfasserIn]
• Verfasst von: Krauter, Jürgen [VerfasserIn]
• Verfasst von: Martens, Uwe [VerfasserIn]
• Verfasst von: Nachbaur, David [VerfasserIn]
• Verfasst von: Abu Samra, Maisun [VerfasserIn]
• Verfasst von: Girschikofsky, Michael [VerfasserIn]
• Verfasst von: Basara, Nadezda [VerfasserIn]
• Verfasst von: Benner, Axel [VerfasserIn]
• Verfasst von: Thol, Felicitas [VerfasserIn]
• Verfasst von: Heuser, Michael [VerfasserIn]
• Verfasst von: Ganser, Arnold [VerfasserIn]
• Verfasst von: Döhner, Konstanze [VerfasserIn]
• Verfasst von: Döhner, Hartmut [VerfasserIn]
• Titel: Gemtuzumab ozogamicin in NPM1-mutated acute myeloid leukemia
• Titelzusatz: early results from the prospective randomized AMLSG 09-09 phase III study
• Verf.angabe: Richard F. Schlenk, MD; Peter Paschka, MD; Julia Krzykalla, MSc; Daniela Weber, MSc; Silke Kapp-Schwoerer, MD; Verena I. Gaidzik, MD; Claudia Leis, BSc; Walter Fiedler, MD; Thomas Kindler, MD; Thomas Schroeder, MD; Karin Mayer, MD; Michael Lübbert, MD; Mohammed Wattad, MD; Katharina Götze, MD; Heinz A. Horst, MD, PhD; Elisabeth Koller, MD; Gerald Wulf, MD; Jan Schleicher, MD; Martin Bentz, MD; Richard Greil, MD; Bernd Hertenstein, MD, PhD; Jürgen Krauter, MD; Uwe Martens, MD; David Nachbaur, MD; Maisun Abu Samra, MD; Michael Girschikofsky, MD; Nadezda Basara, MD, DSc; Axel Benner, Dipl-Stat; Felicitas Thol, MD; Michael Heuser, MD; Arnold Ganser, MD; Konstanze Döhner, MD; and Hartmut Döhner, MD
• E-Jahr: 2019
• Jahr: December 18, 2019
• Umfang: 10 S.
• Fussnoten: Gesehen am 08.04.2020
• Titel Quelle: Enthalten in: Journal of clinical oncology
• Ort Quelle: Alexandria, Va. : American Society of Clinical Oncology, 1983
• Jahr Quelle: 2019
• Band/Heft Quelle: 38(2019), 6, Seite 623-632
• ISSN Quelle: 1527-7755
• DOI: doi:10.1200/JCO.19.01406
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1694239357

Abstract

PURPOSEHigh CD33 expression in acute myeloid leukemia (AML) with mutated NPM1 provides a rationale for the evaluation of gemtuzumab ozogamicin (GO) in this AML entity. We conducted a randomized trial to evaluate GO in combination with intensive induction and consolidation therapy in NPM1-mutated AML.PATIENTS AND METHODSBetween May 2010 and September 2017, patients ≥ 18 years old and considered eligible for intensive therapy were randomly assigned up front for induction therapy with idarubicin, cytarabine, etoposide, and all-trans-retinoic acid with or without GO. The early (P = .02) primary end point of event-free survival (EFS) was evaluated 6 months after completion of patient recruitment.RESULTSFive hundred eighty-eight patients were randomly assigned (standard arm, n = 296; GO arm, n = 292). EFS in the GO arm was not significantly different compared with that in the standard arm (hazard ratio, 0.83; 95% CI, 0.65 to 1.04; P = .10). The early death rate during induction therapy was 10.3% in the GO arm and 5.7% in the standard arm (P = .05). Causes of death in both arms were mainly infections. The cumulative incidence of relapse (CIR) in patients achieving a complete remission (CR) or CR with incomplete hematologic recovery (CRi) was significantly reduced in the GO arm compared with the standard arm (P = .005), with no difference in the cumulative incidence of death (P = .80). Subgroup analysis revealed a significant beneficial effect of GO in female, younger (≤ 70 years), and FLT3 internal tandem duplication-negative patients with respect to EFS and CIR.CONCLUSIONThe trial did not meet its early primary end point of EFS, mainly as a result of a higher early death rate in the GO arm. However, in patients achieving CR/CRi after induction therapy, significantly fewer relapses occurred in the GO compared with the standard arm.