Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long-term outcome of patients with early chronic myeloid leukemia in chronic phase.
BACKGROUND
The European LeukemiaNet recommendations for chronic myeloid leukemia (CML) defined a group of patients with suboptimal response to imatinib. The significance of this response was not well defined.


METHODS
The significance of having had a suboptimal response during imatinib therapy among 281 patients with CML treated with standard-dose (n = 73) or high-dose (n = 208) imatinib was investigated.


RESULTS
Rates of suboptimal response at 6, 12, and 18 months were 4%, 8%, and 40%, respectively, and were not influenced by Sokal risk score. Patients with a suboptimal response at 6 months had a significantly lower probability of eventually achieving a complete cytogenetic response (CCyR) compared with those with an optimal response (30% vs 97%; P < .001), and their event-free survival (EFS) and transformation-free survival (TFS) were found to be similar to those with criteria for failure at this time point. Suboptimal response at 12 months defined a group with a similar TFS as those with optimal response, but with worse EFS. In contrast, patients with a suboptimal response at 18 months had outcomes that were similar to those patients with an optimal response. A multivariate analysis confirmed the significance of response category after adjusting for pretreatment characteristics and imatinib dose.


CONCLUSIONS
The results of the current study suggested that suboptimal response was a heterogeneous category, and some patients had an outcome that mirrored that of patients with failed therapy. Interventions aimed at improving this outcome are required.
Alvarado
Yesid
Y
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Kantarjian
Hagop
H
O'Brien
Susan
S
Faderl
Stefan
S
Borthakur
Gautam
G
Burger
Jan
J
Wierda
William
W
Garcia-Manero
Guillermo
G
Shan
Jianqin
J
Cortes
Jorge
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001549:Benzamides; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate