Gemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study
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Gemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study. / Schlenk, Richard F; Paschka, Peter; Krzykalla, Julia; Weber, Daniela; Kapp-Schwoerer, Silke; Gaidzik, Verena I; Leis, Claudia; Fiedler, Walter; Kindler, Thomas; Schroeder, Thomas; Mayer, Karin; Lübbert, Michael; Wattad, Mohammed; Götze, Katharina; Horst, Heinz A; Koller, Elisabeth; Wulf, Gerald; Schleicher, Jan; Bentz, Martin; Greil, Richard; Hertenstein, Bernd; Krauter, Jürgen; Martens, Uwe; Nachbaur, David; Abu Samra, Maisun; Girschikofsky, Michael; Basara, Nadezda; Benner, Axel; Thol, Felicitas; Heuser, Michael; Ganser, Arnold; Döhner, Konstanze; Döhner, Hartmut.
in: J CLIN ONCOL, Jahrgang 38, Nr. 6, 20.02.2020, S. 623-632.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Gemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study
AU - Schlenk, Richard F
AU - Paschka, Peter
AU - Krzykalla, Julia
AU - Weber, Daniela
AU - Kapp-Schwoerer, Silke
AU - Gaidzik, Verena I
AU - Leis, Claudia
AU - Fiedler, Walter
AU - Kindler, Thomas
AU - Schroeder, Thomas
AU - Mayer, Karin
AU - Lübbert, Michael
AU - Wattad, Mohammed
AU - Götze, Katharina
AU - Horst, Heinz A
AU - Koller, Elisabeth
AU - Wulf, Gerald
AU - Schleicher, Jan
AU - Bentz, Martin
AU - Greil, Richard
AU - Hertenstein, Bernd
AU - Krauter, Jürgen
AU - Martens, Uwe
AU - Nachbaur, David
AU - Abu Samra, Maisun
AU - Girschikofsky, Michael
AU - Basara, Nadezda
AU - Benner, Axel
AU - Thol, Felicitas
AU - Heuser, Michael
AU - Ganser, Arnold
AU - Döhner, Konstanze
AU - Döhner, Hartmut
PY - 2020/2/20
Y1 - 2020/2/20
N2 - 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.
AB - 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.
U2 - 10.1200/JCO.19.01406
DO - 10.1200/JCO.19.01406
M3 - SCORING: Journal article
C2 - 31851556
VL - 38
SP - 623
EP - 632
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 6
ER -
