Imatinib discontinuation in chronic phase myeloid leukaemia patients in sustained complete molecular response: A randomised trial of the Dutch–Belgian Cooperative Trial for Haemato-Oncology (HOVON)

• Published in: European journal of cancer (1990) Vol. 49; no. 15; pp. 3242 - 3246
• Main Authors: Thielen, Noortje, van der Holt, Bronno, Cornelissen, Jan J, Verhoef, Gregor E.G, Gussinklo, Titia, Biemond, Bart J, Daenen, Simon M.G, Deenik, Wendy, van Marwijk Kooy, Rien, Petersen, Eefke, Smit, Willem M, Valk, Peter J.M, Ossenkoppele, Gert J, Janssen, Jeroen J.W.M
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.10.2013; Elsevier
• Subjects: Belgium; Benzamides - administration & dosage; Benzamides - adverse effects; Biological and medical sciences; Chronic myeloid leukaemia; Complete molecular response; Discontinuation; Disease-Free Survival; Drug Administration Schedule; Female; Hematology, Oncology and Palliative Medicine; Humans; Imatinib; Imatinib Mesylate; Leukemia, Myeloid, Chronic-Phase - drug therapy; Male; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Recurrence, Local - diagnosis; Netherlands; Pharmacology. Drug treatments; Piperazines - administration & dosage; Piperazines - adverse effects; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Remission Induction; Survival Rate; Treatment Outcome; Tumors; Belgium; Netherlands; Europe; Chronic myeloid leukaemia; Imatinib; Discontinuation; Complete molecular response; Antineoplastic agent; Human; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Chronic myelogenous leukemia; Malignant hemopathy; Malignant tumor; Myeloproliferative syndrome; Cancerology; Clinical trial; Protein-tyrosine kinase; Cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2013.06.018

Abstract Background Tyrosine kinase inhibitors treatment in responding chronic myeloid leukaemia (CML) patients is generally continued indefinitely. In this randomised phase II trial, we investigated whether CML patients in molecular response4.5 (MR4.5 , quantitative reverse-transcription polymerase chain reaction (RQ-PCR)) after previous combination therapy with imatinib and cytarabine may discontinue imatinib treatment safely. Patients and methods Thirty-three patients from the HOVON 51 study with an MR4.5 for at least 2 years who were still on imatinib treatment were randomised between continuation of imatinib (arm A, n = 18) or discontinuation of imatinib (arm B, n = 15). Results After a median follow up of 36 months since randomisation, 3 patients (17%) in arm A and 10 patients (67%) in arm B had a molecular relapse. All 3 relapsing patients in arm A had also stopped imatinib after randomisation. All but one relapsing patient relapsed within 7 months after discontinuation of imatinib. The molecular relapse rate at 12 and 24 months after randomisation was 0% and 6% (arm A) and 53% and 67% (arm B) respectively. As-treated analysis revealed 56% and 61% relapses at 1 and 2 years since cessation in patients who discontinued imatinib, in contrast to 0% of patients who continued imatinib. All evaluable patients remained sensitive to imatinib after reinitiation and regained a molecular response. Conclusion Our data suggest that discontinuation of imatinib is safe in patients with durable MR4.5.