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Chronic myelogenous leukemia

Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib

Leukemia volume 29, pages 1823–1831 (2015)Cite this article

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Abstract

For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.

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Acknowledgements

This study has been supported by GIMEMA Onlus, BolognAIL and European LeukemiaNet (LSHC-CT-2004-503216). The following members of the ‘GIMEMA Working Party on CML’, formerly ‘ICSG on CML’ actively participated in this study, enrolling patients and collecting clinical data: Lucarelli G, Polimeno G (Internal Medicine Unit, ‘F Miulli’ Hospital, Acquaviva delle Fonti, Bari); Ladetto M, Pini M (Department of Hematology, A.O. N. ‘SS. Antonio e Biagio e Cesare Arrigo’, Alessandria); Rupoli S, Scortechini AR (Hematology Department, University of Ancona, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona, Ancona); Galieni P, Bigazzi C (Hematology Unit, Presidio Ospedaliero ‘C e G Mazzoni’, Ascoli Piceno); Cantore N, Palmieri F (Hematology Division, Ospedale Civile ‘San Giuseppe Moscati’, Avellino); Specchia G, Russo Rossi A (Chair of Hematology, University of Bari, Bari); Rambaldi A, Ferrari ML (Hematology Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo); Palandri F, Luatti S, Iacobucci I, Bochicchio MT, Apolinari M, Fogli M, Cervello I (Institute of Hematology ‘Seràgnoli’, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna); Capucci A, Giuliani G (Hematology Unit, Azienda Ospedaliera ‘Spedali Civili’, Brescia); Malpignano A, Girasoli M (Hematology Division, Ospedale ‘Perrino’, Brindisi); Angelucci E, Usala E (Hematology Unit, Ospedale Oncologico ‘A. Businco’, Cagliari); De Biasi E (Hematology Unit, Presidio Ospedaliero Camposampiero, Camposampiero, Padova); Tagariello G, Sartori R (Hematology Unit, ‘San Giacomo’ Hospital, Castelfranco Veneto, Treviso); Di Raimondo F, Vigneri P (Hematology Unit, ‘Ferrarotto’ Hospital, Catania); Molica S, Lentini M (Hematology Unit, ‘Pugliese’ Hospital, Catanzaro); Lanza F, Viganò C (Hematology and BMT Unit, ‘Istituti Ospitalieri di Cremona’ Hospital, Cremona); Grasso M, Rapezzi D (Division of Hematology, ‘Santa Croce e Carle’ Hospital, Cuneo); Cuneo A, Ciccone M (Chair of Hematology, Dipartimento di Scienze Mediche, ‘Arcispedale S Anna’ University Hospital, Ferrara); Bosi A, Gozzini A (Chair of Hematology, University of Firenze, Firenze); Gobbi M, Pierri I (Chair of Hematology, IRCCS San Martino, Genova); Chianese R (Hematology Unit, Ospedali Riuniti ASL TO4, Ivrea, Torino); De Blasio A, Ciccone F (Hematology Unit, Ospedale Civile, Latina); Capochiani E, Pelosini M (Oncology and Hematology Unit, Ospedali Civili, Livorno); Musolino C, Russo S (Division of Hematology, University of Messina, Messina); Cortelezzi A (Oncohematology Unit of the Elderly, Oncohematology Division, IRCCS Ca’ Granda—Maggiore Policlinico Hospital Foundation, Milano); Luppi M, Marasca R (Chair of Hematology, University of Modena and Reggio Emilia, Modena); Pogliani EM, Gambacorti-Passerini C (Department of Hematology, ‘San Gerardo’ Hospital, Monza); Luciano L, Izzo B (Department of Biochemistry and Medical Biotechnologies, ‘Federico II’ University, Napoli); Ferrara F, Annunziata M (Hematology and Bone Marrow Transplantation Unit, ‘Cardarelli’ Hospital, Napoli); Mettivier V, Sessa U (Hematology Unit, ‘Cardarelli’ Hospital, Napoli); Latte G, Noli D (Hematology Unit, ‘San Francesco’ Hospital, Nuoro); Rege-Cambrin G, Fava C (Department of Clinical and Biological Sciences, ‘San Luigi Gonzaga’ University Hospital, Orbassano, TO); Semenzato G, Binotto G (Department of Internal Medicine, University of Padova, Padova); Fabbiano F, Turri D (Hematology Unit, ‘V Cervello’ Hospital, Palermo); Siragusa S, Caracciolo C (Chair of Hematology, University of Palermo, Palermo); Musso M, Porretto F (Oncology and Bone Marrow Transplantation Unit, ‘La Maddalena’ Hospital, Palermo); Cazzola M, Orlandi E (Hematology Unit, ‘S Matteo’ University Hospital, Pavia); Falini B, Falzetti F (Division of Hematology and Clinical Immunology, Department of Medicine, University of Perugia, Perugia); Visani G, Isidori A (Hematology Unit, ‘San Salvatore’ Hospital, Pesaro); Di Bartolomeo P, Di Lorenzo R (Hematology Unit, Ospedale Civile dello Spirito Santo, Pescara); Vallisa D, Trabacchi E (Hematology Division, ‘Guglielmo da Saliceto’ Hospital, Piacenza); Pizzuti M (Hematology Unit, ‘San Carlo’ Hospital, Potenza); Zuffa E, Salvucci M (Hematology Unit, ‘Santa Maria delle Croci’ Hospital, Ravenna); Ronco F, Ielo D (Hematology Unit, Ospedali Riuniti, Reggio Calabria); Merli F, Avanzini P (Hematology Unit, Arcispedale Santa Maria Nuova, Reggio Emilia); Tosi P, Merli A (Hematology Unit, Ospedale Infermi Azienda Unità Sanitaria, Rimini); Sica S, Sorà F, (Istituto di Semeiotica Medica, Università Cattolica del Sacro Cuore-Policlinico ‘Gemelli’, Roma); Latagliata R (Chair of Hematology, ‘La Sapienza’ University, Roma); De Fabritiis P, Trawiska M (Hematology Unit, ‘S. Eugenio’ Hospital, Roma); Amadori S, Cantonetti M (Department of Hematology, ‘Tor Vergata’ University, Roma); Majolino I, Pacilli L (Hematology and Stem Cell Transplantation Unit, Azienda Ospedaliera San Camillo Forlanini, Roma); Ronci B, Cedrone M (Hematology Unit, Ente Ospedaliero San Giovanni Addolorata, Roma); Mengarelli A, Romano A (Hematology Unit, Istituto Regina Elena, Roma); Tafuri A, Montefusco E (Hematology Unit, ‘Sant' Andrea’ Hospital, Roma); Iuliano F, Infusino S (Hematology Unit, Presidio Ospedaliero ‘N Giannettasio’, Rossano Calabro); Dore F, Fozza C (Institute of Hematology, University of Sassari, Sassari); Bocchia M, Defina M (Chair of Hematology, University of Siena, Siena); Liberati AM, Luzi D (Hematology and Oncology Unit, Azienda Ospedaliera ‘S Maria’, Terni); Boccadoro M, Ferrero D (Section of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino) Vitolo U, Nicolosi M (Hematology Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, University of Torino, Torino); Gottardi M, Calistri E (Hematology Unit, ‘Ca' Foncello’ Hospital, Treviso); Fanin R, Tiribelli M (Chair of Hematology, University of Udine, Udine); Pizzolo G, Bonifacio M (Chair of Hematology, University of Verona, Verona); Rodeghiero F, Di Bona E (Hematology Unit, Ospedale Civile, Vicenza).

Author Contributions

FC, MB and GR analyzed the data and wrote the first draft of the manuscript. All the other authors contributed to the design of the study, to the collection of the data and to the final report.

Author information

Authors and Affiliations

  1. Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L and A Seràgnoli', University of Bologna, 'S Orsola-Malpighi' University Hospital, Bologna, Italy

    F Castagnetti, G Gugliotta, C Venturi, S Soverini, N Testoni, M Cavo, G Martinelli & G Rosti

  2. Chair of Hematology, 'La Sapienza' University, Roma, Italy

    M Breccia & G Alimena

  3. Chair of Hematology, University of Catania, Catania, Italy

    F Stagno

  4. Oncohematology Division, Oncohematology of the Elderly Unit, IRCCS Ca’ Granda – Maggiore University Hospital, Milano, Italy

    A Iurlo

  5. Chair of Hematology, University of Bari, Bari, Italy

    F Albano

  6. Hematology Unit, 'S Eugenio' Hospital, Roma, Italy

    E Abruzzese

  7. Hematology Unit, Azienda Ospedaliera 'Bianchi-Melacrino-Morelli', Reggio Calabria, Italy

    B Martino

  8. Hematology Unit, 'Pugliese-Ciaccio' Hospital, Catanzaro, Italy

    L Levato

  9. Hematology Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy

    T Intermesoli

  10. Hematology Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Torino, Italy

    P Pregno

  11. Hematology Unit, Azienda Ospedaliera 'Spedali Civili', Brescia, Italy

    G Rossi

  12. Hematology Unit, 'Ca' Foncello' Hospital, Treviso, Italy

    F Gherlinzoni

  13. Chair of Hematology, Torrette University Hospital, Ancona, Italy

    P Leoni

  14. Chair of Hematology, Azienda Ospedaliero Universitaria Arcispedale S Anna, University of Ferrara, Ferrara, Italy

    F Cavazzini

  15. Department of Biochemistry and Medical Biotechnologies, 'Federico II' University, Napoli, Italy

    F Pane

  16. Department of Clinical and Biological Sciences, Chair of Hematology, 'S Luigi Gonzaga' University Hospital, University of Torino, Orbassano, (TO), Italy

    G Saglio

  17. Department of Hematology and Oncology 'L and A Seràgnoli', University of Bologna, Bologna, Italy

    M Baccarani

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  1. F Castagnetti
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Consortia

on behalf of the GIMEMA CML Working Party

Corresponding author

Correspondence to F Castagnetti.

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Competing interests

FC has acted as a consultant for and received honoraria from Novartis, Bristol-Myers Squibb, Pfizer and ARIAD; GG has acted as a consultant and received honoraria from Novartis and Bristol-Myers Squibb; M Breccia has acted as a consultant for Bristol-Myers Squibb and Novartis, Pfizer, Ariad; EA has acted as a consultant for Novartis and Bristol-Myers Squibb; GM served on the speakers’ bureaus of Novartis, Bristol-Myers Squibb and Pfizer; GR has acted as a consultant for and received honoraria from Novartis; FP received research support from Novartis, served as advisor for Novartis, Bristol-Myers Squibb and ARIAD Pharmaceuticals, and received lecture fees from Novartis and Bristol-Myers Squibb; GS has acted as a consultant for and received honoraria from Bristol-Myers Squibb, Novartis, ARIAD Pharmaceuticals and Celgene; G Rosti has acted as a consultant for Novartis, Bristol-Myers Squibb and ARIAD Pharmaceuticals and served on the speakers’ bureaus of Novartis, Bristol-Myers Squibb and Roche; M Baccarani received honoraria from Novartis, Bristol-Myers Squibb, Pfizer and ARIAD Pharmaceuticals and served on the speakers’ bureaus of Novartis and Bristol-Myers Squibb. The other authors declare no conflict of interest.

Additional information

Members of the GIMEMA Working Party on CML are listed before references.

Supplementary Information accompanies this paper on the Leukemia website

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Castagnetti, F., Gugliotta, G., Breccia, M. et al. Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib. Leukemia 29, 1823–1831 (2015). https://doi.org/10.1038/leu.2015.152

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  • DOI: https://doi.org/10.1038/leu.2015.152

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