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Long-term outcome of imatinib 400 mg compared to imatinib 600 mg or imatinib 400 mg daily in combination with cytarabine or pegylated interferon alpha 2a for chronic myeloid leukaemia: results from the French SPIRIT phase III randomised trial


The STI571 prospective randomised trial (SPIRIT) French trial is a four-arm study comparing imatinib (IM) 400 mg versus IM 600 mg, IM 400 mg + cytarabine (AraC), and IM 400 mg + pegylated interferon alpha2a (PegIFN-α2a) for the front-line treatment of chronic-phase chronic myeloid leukaemia (CML). Long-term analyses included overall and progression-free survival, molecular responses to treatment, and severe adverse events. Starting in 2003, the trial included 787 evaluable patients. The median overall follow-up of the patients was 13.5 years (range 3 months to 16.7 years). Based on intention-to-treat analyses, at 15 years, overall and progression-free survival were similar across arms: 85%, 83%, 80%, and 82% and 84%, 87%, 79%, and 79% for the IM 400 mg (N = 223), IM 600 mg (N = 171), IM 400 mg + AraC (N = 172), and IM 400 mg + PegIFN-α2a (N = 221) arms, respectively. The rate of major molecular response at 12 months and deep molecular response (MR4) over time were significantly higher with the combination IM 400 mg + PegIFN-α2a than with IM 400 mg: p = 0.0001 and p = 0.0035, respectively. Progression to advanced phases and secondary malignancies were the most frequent causes of death. Toxicity was the main reason for stopping AraC or PegIFN-α2a treatment.

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Fig. 1: Flow diagram of all 789 randomised patients.
Fig. 2: Long-term survival evaluation.
Fig. 3: Molecular response over time and survival according to the molecular response.


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The promoter of the SPIRIT trial is the University Hospital of Poitiers. The trial is supported by grants (national PHRC 2003, PHRC 2006, and PHRC 2011) from the French Minister of Health, Novartis, and Roche Pharma. In addition to the authors, the following investigators participated in the SPIRIT trial: Hôpital Necker Enfants Malades, Paris: B. Varet, A. Buzyn; Hôpital Archet 1, Nice: JP. Cassuto; Hôpital Cochin, Paris: D. Bouscary; Centre Hospitalier De La Côte Basque, Bayonne: A. Banos; Hôpital D’instruction Des Armées, Clamart: B. Souleau; Centre Hospitalier Intercommunal-Hôpital Font-Pré, Toulon-La Seyne-Sur-Mer: C. Sohn; Hôpital d’instruction des Armées de Sainte-Anne, Toulon Naval: L Boudin; Centre Antoine Lacassagne, Nice: A. Thyss; Hôpital Lapeyronie de Montpellier: G Cartron; Hôpital de Lens: B. Dupriez; Institut De Cancérologie De La Loire: D. Guyotat, C. Mounier, J. Jaubert; Polyclinique Du Parc, Caen: X. Levaltier; Service d’Onco-Hématologie, AP-HP Hopitaux Universitaires Paris Sud, Hôpital Paul Brousse, Villejuif, France: A. Turhan. We thank Florence Tartarin for technical assistance (collection of the data, data management and centralisation of allocated treatment, Inserm Centre Investigation Clinique 1402), the clinical-trial monitors (Inserm Centre Investigation Clinique 1402) for their contribution and members of the nursing and research staff at the trial centres.

France Intergroupe des Leucémies Myéloïdes Chroniques, Fi-LMC

Francois Guilhot1, Françoise Rigal-Huguet2, Joëlle Guilhot1, Agnès-Paule Guerci-Bresler3, Delphine Rea5, Valérie Coiteux6, Martine Gardembas7, Anne Vekhoff9, Marc Berger11, Laurence Legros14, Philippe Rousselot15, Pascal Lenain17, Martine Escoffre Barbe18, Viviane Dubruille21, Pascale Cony-Makhoul24, Hyacinthe Johnson-Ansah25, Melanie Mercier26, Charbonnier Aude28, Lydia Roy35, Nathalie Cambier42, Jean-Michel Cayuela46, Jean-Claude Chomel47, Marc Delord50, Claude Preudhomme51, Gabriel Etienne52,François-Xavier Mahon52, Franck-Emmanuel Nicolini53

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Correspondence to Francois Guilhot.

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FG received research support from Novartis and Roche, honoraria from Novartis, BMS and Celgene; DR received honoraria from Incyte, Novartis and Pfizer; EJ received an honorarium from Novartis; LL received honoraria from Incyte, Novartis, Janssen and Pfizer; PR received research support from Pfizer and Incyte; AD received honoraria from Janssen, Abvie, Gilead, Roche, and Amgen; PCM received research support from Novartis, Pfizer, and Incyte and honoraria from Novartis and Incyte; GE received an honorarium from Novartis; FXM received honoraria from Novartis and BMS; and FEN received honoraria from Sun Pharma and Novartis and research support from Incyte.

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Members of the France Intergroupe des Leucémies Myéloïdes Chroniques, Fi-LMC are listed below Acknowledgements.

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Guilhot, F., Rigal-Huguet, F., Guilhot, J. et al. Long-term outcome of imatinib 400 mg compared to imatinib 600 mg or imatinib 400 mg daily in combination with cytarabine or pegylated interferon alpha 2a for chronic myeloid leukaemia: results from the French SPIRIT phase III randomised trial. Leukemia 35, 2332–2345 (2021).

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