Journal Article

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

Cayuela, Jean-Michel, Berger, Marc, Caillot, Denis, Gyan, Emmanuel, Chomel, Jean-Claude, Rousselot, Philippe, Rea, Delphine, Santagostino, Alberto, Joly, Bertrand, Maloisel, Frédéric, Guilhot, Joëlle, Fouillard, Loïc, Glaisner, Sylvie, Bulabois, Claude-Eric, Dubruille, Viviane, Mahon, François-Xavier, Penot, Amélie, Etienne, Gabriel, Deconinck, Eric, Muller, Marc, Nicolini, Franck- Emmanuel, Guerci-Bresler, Agnès-Paule, Lenain, Pascal, Zerazhi, Hacene, Delord, Marc, Maisonneuve, Herve, Cony-Makhoul, Pascale, Cambier, Nathalie, Pollet, Bertrand, Alexis, Magda, Charbonnier, Aude, Chapiro, Jacques, Berthou, Christian, Dorvaux, Véronique, Johnson-Ansah, Hyacinthe, Plantier, Isabelle, Lebon, Delphine, Roy, Lydia, Vaida, Iona, Legros, Laurence, Rigal-Huguet, Françoise, Mercier, Melanie, Coiteux, Valérie, Escoffre Barbe, Martine, Guilhot, Francois, Kiladjian, Jean-Jacques, Miclea, Jean-Michel, Vekhoff, Anne, Delmer, Alain, Arkam, Yazid, Gardembas, Martine, Preudhomme, Claude, Ghomari, Kamel, Jourdan, Eric, Lhermitte, Ludovic

2021

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Springer Nature
• Subject: 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