Azacitidine frontline therapy for unfit acute myeloid leukemia patients: clinical use and outcome prediction

F Ramos; S Thépot; L Pleyer; L Maurillo; R Itzykson; J Bargay; R Stauder; A Venditti; V Seegers; V Martínez-Robles; S Burgstaller; C Récher; G Debén; G Gaidano; C Gardin; P Musto; R Greil; F Sánchez-Guijo; P Fenaux; European ALMA Investigators

doi:10.1016/j.leukres.2014.12.013

Azacitidine frontline therapy for unfit acute myeloid leukemia patients: clinical use and outcome prediction

Leuk Res. 2015 Mar;39(3):296-306. doi: 10.1016/j.leukres.2014.12.013. Epub 2014 Dec 31.

Authors

F Ramos¹, S Thépot², L Pleyer³, L Maurillo⁴, R Itzykson⁵, J Bargay⁶, R Stauder⁷, A Venditti⁴, V Seegers⁸, V Martínez-Robles⁹, S Burgstaller¹⁰, C Récher¹¹, G Debén¹², G Gaidano¹³, C Gardin⁸, P Musto¹⁴, R Greil³, F Sánchez-Guijo¹⁵, P Fenaux⁵; European ALMA Investigators

Collaborators

European ALMA Investigators:
Sylvain Thépot, Raphael Itzykson, Valerie Seegers, Christian Récher, Emmanuel Raffoux, Bruno Quesnel, Jacques Delaunay, Thomas Cluzeau, Anne Marfaing Koka, Antoine Béclère, Aspasia Stamatoullas, Henri Becquerel, Marie-Pierre Chaury, Emmanuel Gyan, Stéphane Cheze, Anne Banos, Pierre Morel, Isabelle Plantier, Anne-Laure Taksin, Le Chesnay, Ame Shanti, Laurence Sanhes, Stephane De Botton, Jean Pierre Marolleau, Cécile Pautas, Henri Mondor, Eric Wattel, Francoise Isnard, Agnies Guerci, Norbert Vey, Francois Dreyfus, Norbert Ifrah, Lionel Ades, Claude Gardin, Pierre Fenaux, Fernando Ramos, Violeta Martínez-Robles, Joan Bargay, Guillermo Debén, A Coruña, Ana Garrido, Sant Pau, Javier Casaño, Olga Salamero, Juan Miguel Bergua, Enrique Colado, Regina García, Carmen Pedro, Santiago Redondo, Mar Tormo, Santiago Bonanad, María Díez-Campelo, Manuel Pérez-Encinas, Adolfo de la Fuente, Blanca Xicoy, José Francisco Falantes, Patricia Font, Tomás José González-López, Guillermo Martín-Núñez, Pau Montesinos, Fermín Sánchez-Guijo, Lisa Pleyer, Reinhard Stauder, Sonja Burgstaller, Martin Schreder, Christoph Tinchon, Michael Pfeilstoecker, Susanne Steinkirchner, Thomas Melchardt, Martina Mitrovic, Michael Girschikofsky, Alois Lang, Peter Krippl, Thamer Sliwa, Alexander Egle, Wemer Linkesch, Daniella Voskova, Hubert Angermann, Richard Greil, Luca Maurillo, Adriano Venditti, Alessandra Spagnoli, Gianluca Gaidano, Monia Lunghi, Pellegrino Musto, Giuseppe Pietrantuono, Oreste Villani

Affiliations

¹ Department of Hematology, University Hospital, León, Spain; Institute of Biomedicine (IBIOMED), University of León, Spain. Electronic address: mail@fernandoramosmd.es.
² Department of Blood Diseases/Hematology, CHU, Angers, France.
³ 3rd Med. Dept. with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center; Paracelsus Medical University Hospital Salzburg, Austria.
⁴ Department of Hematology, Tor Vergata Foundation Polyclinic, University of Rome, Italy.
⁵ Department of Hematology, Saint Louis Hospital Paris VII University (APHP), France.
⁶ Department of Hematology, Son Llatzer Hospital, Palma de Mallorca, Spain.
⁷ Department of Internal Medicine V (Hematology and Oncology), Innsbruck Medical University, Innsbruck, Austria.
⁸ Department of Hematology, Avicenne Hospital, Paris XIII University (APHP), Bobigny, France.
⁹ Department of Hematology, University Hospital, León, Spain.
¹⁰ Department of Internal Medicine IV, Wels-Grieskirchen Hospital, Wels, Austria.
¹¹ Department of Hematology, CHU, Toulouse, France.
¹² Department of Hematology, University Hospital, A Coruña, Spain.
¹³ Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
¹⁴ Scientific Direction, IRCCS; Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
¹⁵ Department of Hematology, University Hospital, Salamanca, Spain.

PMID: 25601157
DOI: 10.1016/j.leukres.2014.12.013

Abstract

Hypomethylating agents are able to prolong the overall survival of some patients diagnosed with acute myeloid leukemia. The aim of this study was to evaluate the clinical use of azacitidine as front-line therapy in unfit acute myeloid leukemia (AML) patients and to develop a clinical prediction model to identify which patients may benefit more from the drug. One hundred and ten untreated unfit AML patients received front-line azacitidine therapy in Spain, and response and survival were evaluated in them following European LeukemiaNet (ELN) guidelines. A clinical prediction rule was obtained from this population that was validated and refined in 261 patients treated in France, Austria and Italy. ELN response was achieved in 21.0% of the 371 patients (CI95% 17.0-25.5) and did not depend on bone marrow blast cell percentage. Median overall survival was 9.6 months (CI95% 8.5-10.8) and 40.6% of the patients were alive at 1 year (CI95% 35.5-45.7). European ALMA score (E-ALMA), based on performance status, white blood cell counts at azacitidine onset and cytogenetics, discriminated three risk groups with different survival and response rates. Azacitidine seems a reasonable therapeutic option for most unfit AML patients, i.e. those displaying a favorable or intermediate E-ALMA score.

Keywords: Acute myeloid leukemia; Azacitidine; Elderly; Prediction; Score; Unfit.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic / therapeutic use*
Azacitidine / therapeutic use*
Female
Follow-Up Studies
Humans
Leukemia, Myeloid, Acute / drug therapy*
Leukemia, Myeloid, Acute / mortality
Male
Middle Aged
Remission Induction
Retrospective Studies
Survival Rate
Treatment Outcome
Validation Studies as Topic

Substances

Antimetabolites, Antineoplastic
Azacitidine