Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib

Carlo Gambacorti-Passerini*, Laura Antolini, Franois Xavier Mahon, Francois Guilhot, Michael Deininger, Carmen Fava, Arnon Nagler, Chiara Maria Della Casa, Enrica Morra, Elisabetta Abruzzese, Anna D'Emilio, Fabio Stagno, Philipp Le Coutre, Rafael Hurtado-Monroy, Valeria Santini, Bruno Martino, Fabrizio Pane, Andrea Piccin, Pilar Giraldo, Sarit AssoulineMuheez A. Durosinmi, Onno Leeksma, Enrico Maria Pogliani, Miriam Puttini, Eunjung Jang, Josy Reiffers, Maria Grazia Valsecchi, Dong Wook Kim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


BackgroundImatinib slows development of chronic myeloid leukemia (CML). However, available information on morbidity and mortality is largely based on sponsored trials, whereas independent long-term field studies are lacking.Patients and MethodsConsecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission (CCyR) after 2 years (±3 months) were eligible for enrollment in the independent multicenter Imatinib Long-Term (Side) Effects (ILTE) study. Incidence of the first serious and nonserious adverse events and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the standard log-rank test. Attainment of negative Philadelphia chromosome hematopoiesis was assessed with cytogenetics and quantitative polymerase chain reaction. Cumulative incidence of death related or unrelated to CML progression was estimated, accounting for competing risks, according to the Kalbleisch-Prentice method. Standardized incidence ratios were calculated based on population rates specific for sex and age classes. Confidence intervals were calculated by the exact method based on the χ2 distribution. All statistical tests were two-sided.ResultsA total of 832 patients who were treated for a median of 5.8 years were enrolled. There were 139 recorded serious adverse events, of which 19.4% were imatinib-related. A total of 830 nonserious adverse events were observed in 53% of patients; 560 (68%) were imatinib-related. The most frequent were muscle cramps, asthenia, edema, skin fragility, diarrhea, tendon, or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxic effects. Forty-five patients lost CCyR, at a rate of 1.4 per 100 person-years. Durable (>1 year) negative Philadelphia chromosome hematopoiesis was attained by 179 patients. Twenty deaths were observed, with a 4.8% mortality incidence rate (standardized incidence ratio = 0.7; 95% confidence interval = 0.40 to 1.10, P =. 08), with only six (30%) associated with CML progression.ConclusionsIn this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.

Original languageEnglish
Pages (from-to)553-561
Number of pages9
JournalJournal of the National Cancer Institute
Issue number7
StatePublished - 6 Apr 2011
Externally publishedYes


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