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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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
December 18, 2019
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| In: |
Journal of clinical oncology
Year: 2019, Volume: 38, Issue: 6, Pages: 623-632 |
| ISSN: | 1527-7755 |
| DOI: | 10.1200/JCO.19.01406 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1200/JCO.19.01406 Verlag, lizenzpflichtig, Volltext: https://ascopubs.org/doi/10.1200/JCO.19.01406 
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| Author Notes: | 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 |
MARC
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| 245 | 1 | 0 | |a Gemtuzumab ozogamicin in NPM1-mutated acute myeloid leukemia |b early results from the prospective randomized AMLSG 09-09 phase III study |c 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 |
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| 520 | |a 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. | ||
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