Arsenic Trioxide and All-Trans Retinoic Acid Combination Therapy for the Treatment of High-Risk Acute Promyelocytic Leukemia: Results From the APOLLO Trial
Abstract
PURPOSE The phase III APOLLO trial prospectively compared the efficacy of arsenic trioxide (ATO) in combination with all-trans retinoic acid (ATRA) regimen (ATRA and ATO [ATRA-ATO]) plus low-dose idarubicin versus standard ATRA plus anthracycline-based chemotherapy (ATRA-CHT) regimen (ie, ATRA and idarubicin regimen) in patients with high-risk acute promyelocytic leukemia (APL; EudraCT 2015-01151-68; ClinicalTrials.gov identifier: NCT02688140 ). METHODS Adult patients with newly diagnosed high-risk APL in the ATRA-ATO arm received ATO 0.15 mg/kg once daily and ATRA 45 mg/m 2 twice daily until complete remission (CR), with two doses of idarubicin 12 mg/m 2 on days 1 and 3, followed by consolidation therapy (four ATRA-ATO cycles). Patients in the ATRA-CHT arm received induction with ATRA 45 mg/m 2 twice daily and idarubicin 12 mg/m 2 once daily on days 1, 3, 5, and 7, followed by three cycles of chemotherapy-based consolidation and 2 years of maintenance therapy. The primary study end point was event-free survival (EFS) at 2 years. RESULTS As of July 2022, 133 eligible patients had received either ATRA-ATO (n = 68) or ATRA-CHT (n = 65). The study was discontinued prematurely because of slow accrual during the COVID-19 pandemic. After a median follow-up of 37 months (range, 1.7-88.6 months), 2-year EFS was 88% in the ATRA-ATO arm and 71% in the ATRA-CHT arm (HR, 0.4 [95% CI, 0.17 to 0.92]; log-rank test P = .02). At a median of 7.8 and 12.1 months from achievement of CR, molecular relapse occurred in one (1.5%) ATRA-ATO patient versus eight (12.3%) ATRA-CHT patients ( P = .014). Overall, 32% and 68% of patients receiving ATRA-ATO and ATRA-CHT, respectively, reported serious treatment-emergent adverse events ( P < .01). CONCLUSION The results of the APOLLO trial support the use of ATO and ATRA for the treatment of newly diagnosed patients with high-risk APL.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (55)
Uwe Platzbecker
Lionel Adès
Pau Montesinos
Hospital Universitari i Politecnic La Fe, Valencia, Spain
Emanuele Ammatuna
Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
Pierre Fenaux
Claudia Baldus
7Department of Hematology, Kiel University Hospital, Kiel, Germany
Massimo Bernardi
Céline Berthon
29Service d’Hématologie, Centre Hospitalier Universitaire de Lille, Hôpital Claude-Huriez, Lille, France
Monica Bocchia
1Hematology Unit, University of Siena, Siena, Italy
Caroline Bonmati
19Department of Hematology, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France
Erika Borlenghi
10ASST Spedali Civili of Brescia, Department of Hematology, Brescia, Italy
Martin Bornhäuser
Diana Carp
Service d'Hématologie Clinique et de Thérapie Cellulaire, Le Centre Hospitalier Régional d'Orléans, Orléans, France
Sylvain Chantepie
10Department of Hematology, Centre Hospitalier Universitaire de Caen, Caen, France
Enrico Crea
Fondazione GIMEMA Franco Mandelli Onlus, Roma, Italy
Mariadomenica Divona
27University of Rome Tor Vergata, Department of Biomedicine and Prevention, Rome, Italy
Hartmut Döhner
1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Gerhard Ehninger
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Jordi Esteve Reyner
Jamilé Frayfer
30Hôpital de Meaux, Departement of Hematology, Meaux, France
Ana Garrido Diaz
Servicio de Hematología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Cristina Gil
Hospital Alicante, alicante, Spain
Luca Guarnera
Anna Franziska Hamm
Maël Heiblig
9Department of Hematology, Centre Hospitalier Universitaire de Lyon, Lyon, France
Daniela Heidenreich
12Universitätsmedizin Mannheim, Mannheim, Germany
Alwin Johannes Krämer
Department of Internal Medicine 5, University Hospital Heidelberg, Heidelberg, Germany
Marie-Pierre Ledoux
Institut de cancérologie Strasbourg Europe, Strasbourg, France
Monia Lunghi
15Division of Hematology, Department of Translational Medicine, AOU Maggiore della Carità, University of Eastern Piedmont, Novara, Italy
Valentina Mancini
7ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
Klaus Metzeler
4Department of Hematology, Cell Therapy, Hemostaseology and Infectious Diseases, University of Leipzig, Leipzig, Germany
Maria Cristina Miggiano
Azienda ULSS 8 Bercia, Ematologia, Vicenza, Italy
Carsten Müller-Tidow
Pierre Peterlin
12Department of Hematology, Centre Hospitalier Universitaire de Nantes, Nantes, France
Alfonso Piciocchi
4GIMEMA, Rome, Italy
Kathrin Rieger
6Department of Hematology, Oncology, and Tumor Immunology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Christoph Röllig
22Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany
Giovanni Rossi
Ospedale Casa Sollievo della Sofferenza, Ematologia, San Giovanni Rotondo, Italy
Miguel A. Sanz
32Hematology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain and CIBERONC, Instituto de Salud Carlos III, Madrid, Spain
Hubert Serve
Maaike Söhne
St Antonius Ziekenhuis, Nieuwegein, the Netherlands
Karsten Spiekermann
Ludwig Maximilian University Hospital, Munich, Germany
Emmanuelle Tavernier-Tardy
Institut De Cancérologie Et D'hématologie Universitaire De Saint-Étienne, Saint-Priest-en-Jarez, France
Christian Thiede
7University Hospital, Dresden University of Technology, Dresden, Germany
Susana Vives Polo
Servicio de Hematología, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain
Wichard Vogel
7Department of Hematology and Oncology, Eberhard-Karls University, Tübingen, Germany
Patrizia Zappasodi
7Dipartimento di Oncoematologia, Fondazione IRCCS Policlinico San Matteo., Pavia, Italy
Pauline Ziller-Walter
University Hospital Carl Gustav Carus and TU Dresden - Faculty of Medicine, Medical Clinic 1, Dresden, Germany
Maria Teresa Voso
Fatiha Chermat
12Groupe Francophone des Myelodysplasies, Paris, France
Livia Gorreo Renzulli
4Fondazione GIMEMA, Roma, Italy
Madlen Jentzsch
19Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Disease, University of Leipzig Medical Center, Leipzig, Germany
Dietger Niederwieser
2University of Pennsylvania & Penn Medicine, Pennsylvania, United States
Michaela Weier
Sven Zukunft