Improved OutcomesWith 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

被引：289

作者：

Platzbecker, Uwe ^{[1
,2
]}

Avvisati, Giuseppe ^{[14
]}

Cicconi, Laura ^{[15
]}

Thiede, Christian ^{[1
]}

Paoloni, Francesca ^{[16
]}

Vignetti, Marco ^{[16
,17
]}

Ferrara, Felicetto ^{[18
]}

Divona, Mariadomenica ^{[15
]}

Albano, Francesco ^{[19
]}

Efficace, Fabio ^{[16
]}

Fazi, Paola ^{[16
]}

Sborgia, Marco ^{[20
]}

Di Bona, Eros ^{[21
]}

Breccia, Massimo ^{[17
]}

Borlenghi, Erika ^{[22
]}

Cairoli, Roberto ^{[23
]}

Rambaldi, Alessandro ^{[26
]}

Melillo, Lorella ^{[27
]}

La Nasa, Giorgio ^{[28
]}

Fiedler, Walter ^{[3
]}

Brossart, Peter

Hertenstein, Bernd ^{[5
]}

Salih, Helmut R. ^{[6
]}

Wattad, Mohammed ^{[7
]}

Luebbert, Michael ^{[8
]}

Brandts, Christian H. ^{[9
]}

Haenel, Mathias ^{[10
]}

Roellig, Christoph ^{[1
]}

Schmitz, Norbert ^{[4
]}

Link, Hartmut ^{[11
]}

Frairia, Chiara ^{[29
]}

Pogliani, Enrico Maria

Fozza, Claudio ^{[30
]}

D'Arco, Alfonso Maria ^{[31
]}

Di Renzo, Nicola ^{[32
]}

Cortelezzi, Agostino ^{[24
,25
]}

Fabbiano, Francesco ^{[33
]}

Doehner, Konstanze

Ganser, Arnold ^{[13
]}

Doehner, Hartmut

Amadori, Sergio ^{[15
]}

Mandelli, Franco ^{[16
]}

Ehninger, Gerhard ^{[1
,2
]}

Schlenk, Richard F. ^{[12
]}

Lo-Coco, Francesco ^{[15
]}

机构：

[1] Tech Univ Dresden, Univ Klinikum Carl Gustav Carus, Dresden, Germany

[2] Study Alliance Leukemia, Dresden, Germany

[3] Univ Hosp Hamburg Eppendorf, Hamburg, Germany

[4] Asklepios Klin St Georg Hamburg, Hamburg, Germany

[5] Klinikum Bremen Mitte, Bremen, Germany

[6] Univ Hosp Tubingen, Essen, Germany

[7] Kliniken Essen Sud, Essen, Germany

[8] Univ Med Ctr, Freiburg, Germany

[9] Goethe Univ Frankfurt, Frankfurt, Germany

[10] Klinikum Chemnitz gGmbH, Chemnitz, Germany

[11] Westpfalz Klinikum, Klin Innere Med 1, Kaiserslautern, Germany

[12] Univ Hosp Ulm, Ulm, Germany

[13] Hannover Med Sch, Hannover, Germany

[14] Univ Campus Biomed, Rome, Italy

[15] Univ Tor Vergata, Rome, Italy

[16] Grp Italiano Malattie Ematol, Adulto Cent Off, Rome, Italy

[17] Sapienza Univ, Rome, Italy

[18] Cardarelli Hosp, Naples, Italy

[19] Univ Bari, Bari, Italy

[20] UO Ematol Clin, Pescara, Italy

[21] San Bortolo Hosp, Vicenza, Italy

[22] UO Ematol, Spedali Civili, Brescia, Italy

[23] Osped Niguarda Ca Granda, SC Ematol, Milan, Italy

[24] Osped Maggiore Policlin, Fdn Ist Ricovero Cura Carattere Sci Ca Granda, Milan, Italy

[25] Univ Milan, Milan, Italy

[26] Azienda Opsed Papa Giovanni XXIII, Bergamo, Italy

[27] IRCCS, Casa Sollievo Sofferenza Hosp, San Giovanni Rotondo, Italy

[28] Univ Cagliari, Osped R Binaghi, Ctr Trapianti Midollo Osseo, Cagliari, Italy

[29] Citta Salute & Sci, Hematol, Turin, Italy

[30] Univ Sassari, Sassari, Italy

[31] UO Med Interna & Oncoematol PO Umberto I, Nocera Inferiore, Nocera Inferior, Italy

[32] Osped Vito Fazzi, Lecce, Italy

[33] Osped Riuniti Villa Sofia Cervello, Palermo, Italy

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2017年 / 35卷 / 06期

关键词：

FRONT-LINE THERAPY; CONSOLIDATION THERAPY; ANTHRACYCLINE; MANAGEMENT;

D O I：

10.1200/JCO.2016.67.1982

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 firstline 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 3 109/ 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 50months 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 ofmolecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRACHT 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. (C) 2016 by American Society of Clinical Oncology

引用

页码：605 / +

页数：14

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