TY - JOUR
T1 - Gemtuzumab ozogamicin in NPM1-mutated acute myeloid leukemia
T2 - 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 - Samra, Maisun Abu
AU - Girschikofsky, Michael
AU - Basara, Nadezda
AU - Benner, Axel
AU - Thol, Felicitas
AU - Heuser, Michael
AU - Ganser, Arnold
AU - Döhner, Konstanze
AU - Döhner, Hartmut
N1 - Publisher Copyright:
© 2019 by American Society of Clinical Oncology.
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.
UR - http://www.scopus.com/inward/record.url?scp=85080041033&partnerID=8YFLogxK
U2 - 10.1200/JCO.19.01406
DO - 10.1200/JCO.19.01406
M3 - Article
C2 - 31851556
AN - SCOPUS:85080041033
SN - 0732-183X
VL - 38
SP - 623
EP - 632
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 6
ER -