Open AccessGemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study
Author(s) -
Richard F. Schlenk,
Peter Paschka,
Julia Krzykalla,
Daniela Weber,
Silke Kapp-Schwoerer,
Verena I. Gaidzik,
Claudia Leis,
Walter Fiedler,
Thomas Kindler,
Thomas Schroeder,
Karin Mayer,
Michael Lübbert,
Mohammed Wattad,
Katharina Götze,
Heinz A. Horst,
Elisabeth Koller,
Gerald Wulf,
Jan Schleicher,
Martin Bentz,
Richard Greil,
Bernd Hertenstein,
Jürgen Krauter,
Uwe M. Martens,
David Nachbaur,
Maisun Abu Samra,
Michael Girschikofsky,
Nadežda Basara,
Axel Benner,
Felicitas Thol,
Michael Heuser,
Arnold Ganser,
Konstanze Döhner,
Hartmut Döhner
Publication year - 2020
Publication title -
journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.482
H-Index - 548
eISSN - 1527-7755
pISSN - 0732-183X
DOI - 10.1200/jco.19.01406
Subject(s) - gemtuzumab ozogamicin , medicine , idarubicin , cumulative incidence , cytarabine , myeloid leukemia , etoposide , npm1 , oncology , acute promyelocytic leukemia , surgery , hazard ratio , gastroenterology , cohort , chemotherapy , confidence interval , cd33 , retinoic acid , biochemistry , genetics , chemistry , stem cell , karyotype , cd34 , gene , chromosome , biology
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.