Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV

• Published in: Leukemia Vol. 29; no. 5; pp. 1123 - 1132
• Main Authors: Kalmanti, L, Saussele, S, Lauseker, M, Müller, M C, Dietz, C T, Heinrich, L, Hanfstein, B, Proetel, U, Fabarius, A, Krause, S W, Rinaldetti, S, Dengler, J, Falge, C, Oppliger-Leibundgut, E, Burchert, A, Neubauer, A, Kanz, L, Stegelmann, F, Pfreundschuh, M, Spiekermann, K, Scheid, C, Pfirrmann, M, Hochhaus, A, Hasford, J, Hehlmann, R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2015; Nature Publishing Group
• Subjects: 38/77; 631/154/436/108; 692/308/2779/777; 692/699/1541/1990/2331; 692/699/67/1059/99; 692/699/67/1990/283/1896; Aged; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Benzamides - administration & dosage; Benzamides - adverse effects; Cancer Research; Care and treatment; Chronic myeloid leukemia; Critical Care Medicine; Cytogenetics; Diagnosis; Disease Progression; Disease-Free Survival; Drug dosages; Female; Follow-Up Studies; Fusion Proteins, bcr-abl - genetics; Fusion Proteins, bcr-abl - metabolism; Health aspects; Hematology; Humans; Imatinib; Imatinib Mesylate; Inhibitor drugs; Intensive; Interferon; Interferon-alpha - therapeutic use; Internal Medicine; Kinases; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Male; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Myeloid leukemia; Oncology; original-article; Patients; Pilot Projects; Piperazines - administration & dosage; Piperazines - adverse effects; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein-tyrosine kinase; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Randomization; Remission; Remission Induction; Response rates; Safety; Side effects; Survival; Toxicity; Treatment Outcome; Tyrosine; α-Interferon; United States
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2015.36

Tyrosine kinase inhibitors (TKI) have changed the natural course of chronic myeloid leukemia (CML). With the advent of second-generation TKI safety and efficacy issues have gained interest. The randomized CML - Study IV was used for a long-term evaluation of imatinib (IM). 1503 patients have received IM, 1379 IM monotherapy. After a median observation of 7.1 years, 965 patients (64%) still received IM. At 10 years, progression-free survival was 82%, overall survival 84%, 59% achieved MR 5 , 72% MR 4.5 , 81% MR 4 , 89% major molecular remission and 92% MR 2 (molecular equivalent to complete cytogenetic remission). All response levels were reached faster with IM800 mg except MR 5 . Eight-year probabilities of adverse drug reactions (ADR) were 76%, of grades 3–4 22%, of non-hematologic 73%, and of hematologic 28%. More ADR were observed with IM800 mg and IM400 mg plus interferon α (IFN). Most patients had their first ADR early with decreasing frequency later on. No new late toxicity was observed. ADR to IM are frequent, but mostly mild and manageable, also with IM 800 mg and IM 400 mg+IFN. The deep molecular response rates indicate that most patients are candidates for IM discontinuation. After 10 years, IM continues to be an excellent initial choice for most patients with CML.