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Gemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study.

Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany. Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany. Division of Biostatistics, German Cancer Research Center Heidelberg, Heidelberg, Germany. Department of Internal Medicine II, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Department of Hematology, Medical Oncology and Pneumology, University Medical Center Mainz, Mainz, Germany. Department of Hematology, Oncology, and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany. Internal Medicine III, University Hospital of Bonn, Bonn, Germany. Klinik für Innere Medizin I, Universitätsklinikum Freiburg, Freiburg, Germany. Department of Hematology and Oncology, Hospital Essen-Werden, Essen, Germany. Department of Internal Medicine III, University Hospital Klinikum Rechts der Isar, Munich, Germany. Department of Internal Medicine II, University Hospital of Schleswig-Holstein, Kiel, Germany. Department of Internal Medicine III, Hanuschkrankenhaus Wien, Wien, Austria. Department of Hematology and Oncology, University Hospital of Göttingen, Göttingen, Germany. Klinikum der Landeshauptstadt Stuttgart, Stuttgart, Germany. Department of Hematology and Oncology, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany. IIIrd Medical Department, Paracelsus Medical University Salzburg; Salzburg Cancer Research Institute; and Cancer Cluster Salzburg, Salzburg, Austria. Department of Hematology and Oncology, Klinikum Bremen Mitte, Bremen, Germany. Department Hematology and Oncology, Braunschweig Municipal Hospital, Braunschweig, Germany. Department of Hematology and Oncology, Klinikum am Gesundbrunnen, Heilbronn, Germany. Department of Internal Medicine V, University Hospital of Innsbruck, Innsbruck, Austria. Department of Internal Medicine IV, University Hospital of Gießen, Gießen, Germany. Department of Hematology and Oncology, Hospital Elisabethinen Linz, Linz, Austria. Department of Hematology and Oncology, Malteser Krankenhaus St Franziskus-Hospital, Flensburg, Germany. Department of Hematology, Hemostaseology, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020;(6):623-632
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Abstract

PURPOSE High 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 METHODS Between 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. RESULTS Five 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. CONCLUSION The 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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