Journal Article

DKFZ-2020-01703

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Impact of gemtuzumab ozogamicin on MRD and relapse risk in NPM1 mutated AML patients: results from the AMLSG 09-09 Trial.

Kapp-Schwoerer, S. ; Weber, D. ; Corbacioglu, A. ; Gaidzik, V. I. ; Paschka, P. ; Krönke, J. ; Theis, F. ; Rücker, F. G. ; Teleanu, M.-V.DKFZ* ; Panina, E. ; Jahn, N. ; Herzig, J. K. ; Kubanek, L. ; Schrade, A. ; Gohring, G. ; Fiedler, W. ; Kindler, T. ; Schroeder, T. ; Mayer, K. ; Lübbert, M. ; Wattad, M. ; Götze, K. ; Horst, H. A. ; Koller, E. ; Wulf, G. G. ; Schleicher, J. ; Bentz, M. ; Krauter, J. ; Bullinger, L. ; Krzykalla, J.DKFZ* ; Benner, A.DKFZ* ; Schlenk, R. F. ; Thol, F. ; Heuser, M. ; Ganser, A. ; Döhner, H. ; Döhner, K.

2020
HighWire Press Stanford, Calif.

This record in other databases:  

Please use a persistent id in citations: doi:10.1182/blood.2020005998

Abstract: Monitoring of measurable residual disease (MRD) provides prognostic information in patients with Nucleophosmin1 mutated (NPM1mut) acute myeloid leukemia (AML) and represents a powerful tool to evaluate treatment effects within clinical trials. We determined NPM1mut transcript levels (TL) by RQ-PCR and evaluated the prognostic impact of NPM1mut MRD and the effect of gemtuzumab ozogamicin (GO) on NPM1mut TL and the cumulative incidence of relapse (CIR) in patients with NPM1mut AML enrolled in the randomized phase III AMLSG 09-09 trial. 3733 bone marrow (BM) and 3793 peripheral blood (PB) samples from 469 patients were analyzed. NPM1mut TL log10 reduction ≥3 and achievement of MRD negativity in BM and PB were significantly associated with a lower CIR rate, after two treatment cycles and at end of treatment (EOT). In multivariate analyses, MRD positivity consistently revealed as poor prognostic factor in BM and PB. With regard to treatment effect, the median NPM1mut TL were significantly lower in the GO-Arm across all treatment cycles, resulting in a significantly higher proportion of patients achieving MRD negativity at EOT (56% vs 41%; P=.01). The betterreduction of NPM1mut TL after two treatment cycles in MRD-positive patients by the addition of GO led to a significantly lower CIR rate (4-year CIR 29.3% vs 45.7%, P=.009). In conclusion, the addition of GO to intensive chemotherapy in NPM1mut AML resulted in a significantly better reduction of NPM1mut TL across all treatment cycles leading to a significantly lower relapse rate. The AMLSG 09-09 trial was registered at www.clinicaltrials.gov as #NCT00893399.

Note: 2020 Dec 24;136(26):3041-3050

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Contributing Institute(s):

1. C060 Biostatistik (C060)
2. Translationale Medizinische Onkologie (B340)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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