Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-alpha: follow-up results.
We treated 261 patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) in chronic phase after failure of IFN-alpha with the Bcr-Abl tyrosine kinase inhibitor imatinib mesylate (400 mg/day given p.o.) and analyzed hematological and cytogenetic responses, long-term prognosis, factors associated with achievement of major cytogenetic response and survival, and comparative survival in similar patients treated with other regimens. Median patient age was 55 years; 34% were 60 years or older, and median chronic-phase duration was 33 months. Overall, 94% achieved a complete hematological response, and 71% had a cytogenetic response [major (Ph+ cells <35%) in 62% and complete in 45%]. At a median follow-up of 17 months, 241 patients (92%) were still taking imatinib mesylate; estimated 18-month freedom from progression and survival rates were 93 and 96%. Multivariate analysis of factors associated with major cytogenetic response identified long chronic phase, marrow basophilia, high percentage of Ph+ cells before therapy, and prior hematological resistance to IFN-alpha as being adverse factors. This model was used to generate good-, intermediate- and poor-risk subgroups who had estimated major cytogenetic response rates of 93, 53, and 34%, respectively. Univariate analysis in terms of survival identified leukocytosis, high percentages of peripheral and marrow blasts, marrow basophilia, and the presence of cytogenetic clonal evolution as being adverse factors. Achieving a cytogenetic response at 3 or 6 months of therapy was associated with prolonged survival. In a subset analysis, survival rates among 161 patients with Ph-positive CML after hematological or cytogenetic failure after IFN-alpha who had been treated with imatinib mesylate were better than those for similar patients treated previously with other regimens. In summary, imatinib mesylate is highly effective in chronic-phase CML after IFN-alpha failure. We identified pretreatment and treatment-associated factors that were associated with higher major cytogenetic response rates and with improved survival.
Kantarjian
Hagop M
HM
Departments of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. hkantarj@mdanderson.org
Talpaz
Moshe
M
O'Brien
Susan
S
Smith
Terry L
TL
Giles
Francis J
FJ
Faderl
Stefan
S
Thomas
Deborah A
DA
Garcia-Manero
Guillermo
G
Issa
Jean-Pierre J
JP
Andreeff
Michael
M
Kornblau
Steven M
SM
Koller
Charles
C
Beran
Milosav
M
Keating
Michael
M
Rios
Mary Beth
MB
Shan
Jenny
J
Resta
Debra
D
Capdeville
Renaud
R
Hayes
Kimberly
K
Albitar
Maher
M
Freireich
Emil J
EJ
Cortes
Jorge E
JE
D001549:Benzamides; D002908:Chronic Disease; D020732:Cytogenetic Analysis; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use*; D015996:Survival Rate; D017211:Treatment Failure; D016896:Treatment Outcome
D001549:Benzamides; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases