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

• Published in: Leukemia Vol. 35; no. 8; pp. 2332 - 2345
• Main Authors: Guilhot, Francois, Rigal-Huguet, Françoise, Guilhot, Joëlle, Guerci-Bresler, Agnès-Paule, Maloisel, Frédéric, Rea, Delphine, Coiteux, Valérie, Gardembas, Martine, Berthou, Christian, Vekhoff, Anne, Jourdan, Eric, Berger, Marc, Fouillard, Loïc, Alexis, Magda, Legros, Laurence, Rousselot, Philippe, Delmer, Alain, Lenain, Pascal, Escoffre Barbe, Martine, Gyan, Emmanuel, Bulabois, Claude-Eric, Dubruille, Viviane, Joly, Bertrand, Pollet, Bertrand, Cony-Makhoul, Pascale, Johnson-Ansah, Hyacinthe, Mercier, Melanie, Caillot, Denis, Charbonnier, Aude, Kiladjian, Jean-Jacques, Chapiro, Jacques, Penot, Amélie, Dorvaux, Véronique, Vaida, Iona, Santagostino, Alberto, Roy, Lydia, Zerazhi, Hacene, Deconinck, Eric, Maisonneuve, Herve, Plantier, Isabelle, Lebon, Delphine, Arkam, Yazid, Cambier, Nathalie, Ghomari, Kamel, Miclea, Jean-Michel, Glaisner, Sylvie, Cayuela, Jean-Michel, Chomel, Jean-Claude, Muller, Marc, Lhermitte, Ludovic, Delord, Marc, Preudhomme, Claude, Etienne, Gabriel, Mahon, François-Xavier, Nicolini, Franck- Emmanuel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2021; Nature Publishing Group; Springer Nature
• Subjects: 631/67/1990/2331; 692/308/2779/109/1942; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Research; Chronic myeloid leukemia; Comparative analysis; Critical Care Medicine; Cytarabine; Cytarabine - administration & dosage; Development and progression; Dose-response relationship (Biochemistry); Dose-Response Relationship, Drug; Drug therapy; Female; Follow-Up Studies; Hematology; Human health and pathology; Humans; Imatinib; Imatinib Mesylate - administration & dosage; Inhibitor drugs; Intensive; Interferon; Interferon-alpha - administration & dosage; Internal Medicine; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Life Sciences; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Patients; Polyethylene Glycols - administration & dosage; Prognosis; Prospective Studies; Recombinant Proteins - administration & dosage; Survival; Survival Rate; Targeted cancer therapy; Toxicity; Young Adult; United Kingdom
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-020-01117-w

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.