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J Clin Oncol. 2017 Feb 20;35(6):605-612. doi: 10.1200/JCO.2016.67.1982. Epub 2016 Oct 31.

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.

Author information

1
Uwe Platzbecker, Christian Thiede, Christoph Röllig, and Gerhard Ehninger, Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden; Uwe Platzbecker and Gerhard Ehninger, Study Alliance Leukemia, Dresden; Walter Fiedler, University Hospital Hamburg-Eppendorf; Norbert Schmitz, Asklepios Klinik St Georg Hamburg, Hamburg; Peter Brossart, Innere Medizin mit deSchwerpunkten Onkologie, Haematollogie un Rheumatologie, Bonn; Bernd Hertenstein, Klinikum Bremen Mitte, Bremen; Helmut R. Salih, University Hospital Tubingen; Mohammed Wattad, Kliniken Essen Süd, Essen; Michael Lübbert, University Medical Center, Freiburg; Christian H. Brandts, Goethe University Frankfurt, Frankfurt; Mathias Hänel, Klinikum Chemnitz gGmbH, Chemnitz; Hartmut Link, Klinik für Innere Medizin I, Westpfalz-Klinikum, Kaiserslautern; Konstanze Döhner, Hartmut Döhner, and Richard F. Schlenk, University Hospital Ulm, Ulm; Arnold Ganser, Hannover Medical School, Hannover, Germany; Giuseppe Avvisati, University Campus Bio-Medico; Laura Cicconi, Mariadomenica Divona, Sergio Amadori, and Francesco Lo-Coco, University Tor Vergata; Francesca Paoloni, Marco Vignetti, Fabio Efficace, Paola Fazi, and Franco Mandelli, Gruppo Italiano Malattie Ematologiche dell'Adulto Central Office; Marco Vignetti and Massimo Breccia, Sapienza University, Rome; Felicetto Ferrara, Cardarelli Hospital, Naples; Francesco Albano, University of Bari, Bari; Marco Sborgia, U.O. di Ematologia Clinica, Pescara; Eros Di Bona, San Bortolo Hospital, Vicenza; Erika Borlenghi, U.O. di Ematologia, Spedali Civili, Brescia; Roberto Cairoli, Ospedale Niguarda, Ca' Granda, SC Ematologia; Agostino Cortelezzi, Foundation Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milano; Alessandro Rambaldi, Azienda Opsedaliera Papa Giovanni XXIII, Bergamo; Lorella Melillo, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo; Giorgio La Nasa, Centro Trapianti Midollo Osseo, Ospedale R. Binaghi, Università di Cagliari, Cagliari; Chiara Frairia, Hematology, Città della Salute e della Scienza, Torino; Enrico Maria Pogliani, Ospedale San Gerardo, Università degli Studi Milano Bicocca, Monza; Claudio Fozza, University of Sassari, Sassari; Alfonso Maria D'Arco, U.O. Medicina Interna e Onco-Ematologica P.O. "Umberto I," Nocera Inferiore, Nocera Inferiore; Nicola Di Renzo, Ospedale Vito Fazzi, Lecce; and Francesco Fabbiano, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.

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 × 109/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.

PMID:
27400939
DOI:
10.1200/JCO.2016.67.1982
[Indexed for MEDLINE]
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