Journal Article

DKFZ-2023-01870

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Randomized phase-III study of low-dose cytarabine and etoposide + /- all-trans retinoic acid in older unfit patients with NPM1-mutated acute myeloid leukemia.

Schlenk, R. (First author)DKFZ* ; Weber, D. ; Krzykalla, J.DKFZ* ; Kindler, T. ; Wulf, G. ; Hertenstein, B. ; Salih, H. R. ; Südhoff, T. ; Krauter, J. ; Martens, U. ; Wessendorf, S. ; Runde, V. ; Tischler, H. J. ; Bentz, M. ; Koller, E. ; Heuser, M. ; Thol, F. ; Benner, A.DKFZ* ; Ganser, A. ; Döhner, K. ; Döhner, H.

2023
Macmillan Publishers Limited, part of Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41598-023-41964-y

Abstract: The aim of this randomized clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with non-intensive chemotherapy in older unfit patients (> 60 years) with newly diagnosed NPM1-mutated acute myeloid leukemia. Patients were randomized (1:1) to low-dose chemotherapy with or without open-label ATRA 45 mg/m2, days 8-28; the dose of ATRA was reduced to 45 mg/m2, days 8-10 and 15 mg/m2, days 11-28 after 75 patients due to toxicity. Up to 6 cycles of cytarabine 20 mg/day s.c., bid, days 1-7 and etoposide 100 mg/day, p.o. or i.v., days 1-3 with (ATRA) or without ATRA (CONTROL) were intended. The primary endpoint was overall survival (OS). Between May 2011 and September 2016, 144 patients (median age, 77 years; range, 64-92 years) were randomized (72, CONTROL; 72, ATRA). Baseline characteristics were balanced between the two study arms. The median number of treatment cycles was 2 in ATRA and 2.5 in CONTROL. OS was significantly shorter in the ATRA compared to the CONTROL arm (p = 0.023; median OS: 5 months versus 9.2 months, 2-years OS rate: 7% versus 10%, respectively). Rates of CR/CRi were not different between treatment arms; infections were more common in ATRA beyond treatment cycle one. The addition of ATRA to low-dose cytarabine plus etoposide in an older, unfit patient population was not beneficial, but rather led to an inferior outcome.The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2010-023409-37, first posted 14/12/2010).

Keyword(s): Humans (MeSH) ; Aged (MeSH) ; Etoposide: adverse effects (MeSH) ; Leukemia, Myeloid, Acute: drug therapy (MeSH) ; Leukemia, Myeloid, Acute: genetics (MeSH) ; Cytarabine: adverse effects (MeSH) ; Tretinoin: therapeutic use (MeSH) ; Nuclear Proteins (MeSH) ; Etoposide ; Cytarabine ; Tretinoin ; Nuclear Proteins

Note: #LA:W010#

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Contributing Institute(s):

1. Klinische Studienzentrale (W010)
2. C060 Biostatistik (C060)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2023

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