Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial

Uwe Platzbecker, Giuseppe Avvisati, Laura Cicconi, Christian Thiede, Francesca Paoloni, Marco Vignetti, Felicetto Ferrara, Mariadomenica Divona, Francesco Albano, Fabio Efficace, Paola Fazi, Marco Sborgia, Eros Di Bona, Massimo Breccia, Erika Borlenghi, Roberto Cairoli, Alessandro Rambaldi, Lorella Melillo, Giorgio La Nasa, Walter FiedlerPeter Brossart, Bernd Hertenstein, Helmut R Salih, Mohammed Wattad, Michael Lübbert, Christian H Brandts, Mathias Hänel, Christoph Röllig, Norbert Schmitz, Hartmut Link, Chiara Frairia, Enrico Maria Pogliani, Claudio Fozza, Alfonso Maria D'Arco, Nicola Di Renzo, Agostino Cortelezzi, Francesco Fabbiano, Konstanze Döhner, Arnold Ganser, Hartmut Döhner, Sergio Amadori, Franco Mandelli, Gerhard Ehninger, Richard F Schlenk, Francesco Lo-Coco

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 10(9)/L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively ( P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively ( P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.

Original languageEnglish
Pages (from-to)605-612
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number6
DOIs
Publication statusPublished - Feb 20 2017

Keywords

  • Journal Article

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