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Acute Myeloid Leukemia
Arsenic trioxide is required in the treatment of newly diagnosed acute promyelocytic leukemia. Analysis of a randomized trial (APL 2006) by the French Belgian Swiss APL group
Lionel Adès,1 Xavier Thomas,2 Agnes Guerci Bresler,3 Emmanuel Raffoux,1 Olivier Spertini,4 Norbert Vey,5 Tony Marchand,6 Christian Récher,7 Arnaud Pigneux,8 Stephane Girault,9 Eric Deconinck,10 Claude Gardin,11 Olivier Tournilhac,12 Jean Francois Lambert,13 Patrice Chevallier,14 Stephane de Botton,15 Julie Lejeune,1 Hervé Dombret,1 Sylvie Chevret1 and Pierre Fenaux1
1Hopital Saint Louis, Université Paris Diderot, France; 2Centre Hopitalo-Universitaire Lyon, France; 3Centre Hopitalo-Universitaire Nancy, France; 4Service d'Hématologie CHUV Lausanne, Switzerland; 5Institut Paoli Calmette, Marseille, France; 6Rennes University Hospital, France; 7Toulouse University Hospital, France; 8Bordeaux University Hospital, France; 9Limoges University Hospital, France; 10Besancon University Hospital, France; 11Bobigny University Hospital, France; 12Clermont-Ferrand University Hospital, France; 13Centre Hopitalo-Universitaire Vaudois, Switzerland; 14Nantes University Hospital, France and 15Institut Gustave Roussy, Villejuif, France
ABSTRACT
In standard-risk acute promyelocytic leukemia, recent results have shown that all-trans retinoic acid plus arsenic trioxide combinations are at least as effective as classical all-trans retinoic acid plus anthracy- cline-based chemotherapy while being less myelosuppressive. However, the role of frontline arsenic trioxide is less clear in higher-risk acute promyelocytic leukemia, and access to arsenic remains limited for front- line treatment of standard-risk acute promyelocytic leukemia in many countries. In this randomized trial, we compared arsenic, all-trans retinoic acid and the “classical” cytarabine for consolidation treatment (after all-trans retinoic acid and chemotherapy induction treatment) in standard-risk acute promyelocytic leukemia, and evaluated the addition of arsenic during consolidation in higher-risk disease. Patients with newly diagnosed acute promyelocytic leukemia with a white blood cell count <10x109/L, after an induction treatment consisting of all-trans retinoic acid plus idarubicin and cytarabine, received consolidation chemotherapy with idarubicin and cytarabine, arsenic or all-trans retinoic acid. Patients with a white blood cell count >10x109/L received consolidation chemotherapy with or without arsenic. Overall, 795 patients with acute promyelocytic leukemia were enrolled in this trial. Among those with standard-risk acute promyelocytic leukemia (n=581), the 5-year event-free survival rates from randomization were 88.7%, 95.7% and 85.4% in the cytarabine, arsenic and all-trans retinoic acid consolidation groups, respectively (P=0.0067), and the 5-year cumulative incidences of relapse were was 5.5%, 0% and 8.2%. (P=0.001). Among those with higher-risk acute promyelocytic leukemia (n=214), the 5-year event-free survival rates were 85.5% and 92.1% (P=0.38) in the chemotherapy and chemotherapy plus arsenic groups, respectively, and the corresponding 5-year cumulative incidences of relapse were 4.6% and 3.5% (P=0.99). Given the prolonged myelosuppression that occurred in the chemotherapy plus arsenic arm, a protocol amendment excluded cytarabine during consolidation cycles in the chemotherapy plus arsenic group, resulting in no increase in relapse. Our results there- fore advocate systematic introduction of arsenic in the first-line treat- ment of acute promyelocytic leukemia, but probably not concomitantly with intensive chemotherapy, a situation in which we found myelosup- pression to be significant. (ClinicalTrials.gov Identifier: NCT00378365)
Ferrata Storti Foundation
Haematologica 2018 Volume 103(12):2033-2039
Correspondence:
pierre.fenaux@aphp.fr
Received: May 28, 2018. Accepted: July 17, 2018. Pre-published: July 19, 2018.
doi:10.3324/haematol.2018.198614
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/12/2033
©2018 Ferrata Storti Foundation
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