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Gemtuzumab ozogamicin in NPM1-mutated acute myeloid leukemia: early results from the prospective randomized AMLSG 09-09 phase III study

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...

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Hauptverfasser: Schlenk, Richard Friedrich (VerfasserIn) , Paschka, Peter (VerfasserIn) , Krzykalla, Julia (VerfasserIn) , Weber, Daniela (VerfasserIn) , Kapp-Schwoerer, Silke (VerfasserIn) , Gaidzik, Verena I. (VerfasserIn) , Leis, Claudia (VerfasserIn) , Fiedler, Walter (VerfasserIn) , Kindler, Thomas (VerfasserIn) , Schroeder, Thomas (VerfasserIn) , Mayer, Karin (VerfasserIn) , Lübbert, Michael (VerfasserIn) , Wattad, Mohammed (VerfasserIn) , Götze, Katharina (VerfasserIn) , Horst, Heinz A. (VerfasserIn) , Koller, Elisabeth (VerfasserIn) , Wulf, Gerald (VerfasserIn) , Schleicher, Jan (VerfasserIn) , Bentz, Martin (VerfasserIn) , Greil, Richard (VerfasserIn) , Hertenstein, Bernd (VerfasserIn) , Krauter, Jürgen (VerfasserIn) , Martens, Uwe (VerfasserIn) , Nachbaur, David (VerfasserIn) , Abu Samra, Maisun (VerfasserIn) , Girschikofsky, Michael (VerfasserIn) , Basara, Nadezda (VerfasserIn) , Benner, Axel (VerfasserIn) , Thol, Felicitas (VerfasserIn) , Heuser, Michael (VerfasserIn) , Ganser, Arnold (VerfasserIn) , Döhner, Konstanze (VerfasserIn) , Döhner, Hartmut (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: December 18, 2019
In: Journal of clinical oncology
Year: 2019, Jahrgang: 38, Heft: 6, Pages: 623-632
ISSN:1527-7755
DOI:10.1200/JCO.19.01406
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1200/JCO.19.01406
Verlag, lizenzpflichtig, Volltext: https://ascopubs.org/doi/10.1200/JCO.19.01406
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 08.04.2020
Beschreibung:Online Resource
ISSN:1527-7755
DOI:10.1200/JCO.19.01406

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