TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets

• Published in: Blood 2015-02, Vol.125 (6), p.915-923
• Main Authors: Yeung, David T., Osborn, Michael P., White, Deborah L., Branford, Susan, Braley, Jodi, Herschtal, Alan, Kornhauser, Michael, Issa, Samar, Hiwase, Devendra K., Hertzberg, Mark, Schwarer, Anthony P., Filshie, Robin, Arthur, Christopher K., Kwan, Yiu Lam, Trotman, Judith, Forsyth, Cecily J., Taper, John, Ross, David M., Beresford, Jennifer, Tam, Constantine, Mills, Anthony K., Grigg, Andrew P., Hughes, Timothy P.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Benzamides - administration & dosage; Benzamides - adverse effects; Benzamides - therapeutic use; Clinical Trials and Observations; Female; Fusion Proteins, bcr-abl - analysis; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Male; Middle Aged; Piperazines - administration & dosage; Piperazines - adverse effects; Piperazines - therapeutic use; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Survival Analysis; Treatment Outcome; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2014-07-590315

The Therapeutic Intensification in De Novo Leukaemia (TIDEL)-II study enrolled 210 patients with chronic phase chronic myeloid leukemia (CML) in two equal, sequential cohorts. All started treatment with imatinib 600 mg/day. Imatinib plasma trough level was performed at day 22 and if 10’ BCR-ABL1 at 3 months. Confirmed major molecular response was achieved in 64’ at 12 months and 73’ at 24 months. MR4.5 (BCR-ABL1 ≤0.0032’) at 24 months was 34’. Overall survival was 96’ and transformation-free survival was 95’ at 3 years. This trial supports the feasibility and efficacy of an imatinib-based approach with selective, early switching to nilotinib. This trial was registered at www.anzctr.org.au as ’12607000325404. •Using imatinib to treat CML first-line, with selective nilotinib switching, leads to excellent molecular response and survival.•This strategy may be preferable to universal first-line use of more potent agents, considering efficacy, toxicity, and economic factors.