Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia.
BACKGROUND
The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy.


METHODS
We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events.


RESULTS
The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events.


CONCLUSIONS
After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)
Druker
Brian J
BJ
Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA. drukerb@ohsu.edu
Guilhot
François
F
O'Brien
Stephen G
SG
Gathmann
Insa
I
Kantarjian
Hagop
H
Gattermann
Norbert
N
Deininger
Michael W N
MW
Silver
Richard T
RT
Goldman
John M
JM
Stone
Richard M
RM
Cervantes
Francisco
F
Hochhaus
Andreas
A
Powell
Bayard L
BL
Gabrilove
Janice L
JL
Rousselot
Philippe
P
Reiffers
Josy
J
Cornelissen
Jan J
JJ
Hughes
Timothy
T
Agis
Hermine
H
Fischer
Thomas
T
Verhoef
Gregor
G
Shepherd
John
J
Saglio
Giuseppe
G
Gratwohl
Alois
A
Nielsen
Johan L
JL
Radich
Jerald P
JP
Simonsson
Bengt
B
Taylor
Kerry
K
Baccarani
Michele
M
So
Charlene
C
Letvak
Laurie
L
Larson
Richard A
RA
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000097:blood; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl