Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis.
OBJECTIVE
Imatinib is remarkably effective in treating newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase (CP). To date, most of the available data come from a single multicenter study in which some of the patients were censored for diverse reasons. Here, we report our experience in treating patients at a single institution in a setting where all events were recorded.


METHODS
A total of 204 consecutive adult patients with newly diagnosed CML in CP received imatinib from June 2000 until August 2006. Response (hematologic, cytogenetic, and molecular), progression-free survival (PFS) and survival were evaluated.


RESULTS
At 5 years, cumulative incidences of complete cytogenetic response (CCyR) and major molecular response (MMR) were 82.7% and 50.1%, respectively. Estimated overall survival and PFS were 83.2% and 82.7%, respectively. By 5 years, 25% of patients had discontinued imatinib treatment because of an unsatisfactory response and/or toxicity. The 5-year probability of remaining in major cytogenetic response while still receiving imatinib was 62.7%. Patients achieving a CCyR at 1 year had a better PFS and overall survival than those failing to reach CCyR, but achieving a MMR conferred no further advantage. The identification of a kinase domain mutation was the only factor predicting for loss of CCyR.


CONCLUSIONS
Imatinib is highly effective in most patients with CML-CP; patients who respond are likely to live substantially longer than those treated with earlier therapies. Achieving CCyR correlated with PFS and overall survival, but achieving MMR had no further predictive value. However, approximately one third of patients still need better therapy.
Department of Haematology, Imperial College London, Du Cane Rd, London W12 0NN, United Kingdom.
Hugues
H
de Lavallade
Jane F
JF
Apperley
Jamshid S
JS
Khorashad
Dragana
D
Milojkovic
Alistair G
AG
Reid
Marco
M
Bua
Richard
R
Szydlo
Eduardo
E
Olavarria
Jaspal
J
Kaeda
John M
JM
Goldman
David
D
Marin
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D001854:Bone Marrow Cells / Q000473:pathology*; D015331:Cohort Studies; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000008:administration & dosage*; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate