Imatinib: a second look. Longer follow-up in chronic myeloid leukaemia: clear advantages.

(1) In 2002/2003, the clinical evaluation of imatinib, a tyrosine kinase inhibitor, in the treatment of chronic myeloid leukaemia left many questions unanswered. This article examines data published since then; (2) The only new data on first-line efficacy are the 5-year results of an unblinded trial comparing imatinib versus the interferon plus cytarabine combination. The survival rate was 89% with imatinib, versus about 70% in previous clinical trials of interferon plus cytarabine. Fewer than 2% of patients relapsed after responding to imatinib; (3) As second-line treatment for patients in the chronic phase, we now have non-comparative follow-up data on 532 patients in whom interferon had failed. At 5 years the overall survival rate was 79%, versus about 50% with standard treatments; (4) As second-line treatment for patients in the accelerated phase, we now have non-comparative follow-up data on 235 patients. After 3 years 55% of the patients were still alive, while the usual survival time is 3 to 18 months; (5) As second-line treatment of the blast crisis, we now have non-comparative follow-up data on 260 patients. After 3 years 14% of the patients were still alive, while the usual survival time for patients at this stage is 2 to 4 months; (6) The only new study is a non-comparative follow-up study of 50 children and adolescents aged 2 to 19 years treated with imatinib. The estimated 2-year survival rate was 84%. The haematological and cytogenetic response rates were similar to those reported in adults; (7) The initial clinical evaluation of imatinib showed that its main adverse effects were nausea and vomiting, oedema, fluid retention, muscle cramps, and cutaneous disorders. It was estimated that heart failure occurred in 1 to 10 per 1000 patients. A study of 54 patients confirmed the high incidence of cutaneous disorders. Cases of prostate and bladder cancer have been reported in patients treated with imatinib in France. A study of 16 patients suggests that imatinib might alter bone metabolism; (8) In France, treatment with imatinib costs about 25% more than the interferon plus cytarabine combination; (9) In practice, imatinib seems to increase survival time when used as a first-line or second-line treatment for patients in different phases of chronic myeloid leukaemia. Adverse effects must continue to be closely monitored.