Phase IV study evaluating efficacy of escalated dose of imatinib in chronic myeloid leukemia patients showing suboptimal response to standard dose imatinib.
The aim of this phase IV study was to (1) to define efficacy of escalating dose imatinib in chronic myeloid leukemia (CML) patients showing suboptimal response to standard dose imatinib and (2) to find markers that predict the response to escalating doses of imatinib. CML patients in chronic phase (CP) who failed to achieve optimal response with 400 mg/day imatinib or patients in accelerated phase (AP) or blast crisis (BC) who failed to achieve complete hematologic response after 3 months of 400-600 mg/day imatinib were enrolled. CP patients received 600 mg/day, while AP/BC patients received 600-800 mg/day imatinib. Patients received imatinib for at least 12 months or until the disease progression or intolerable toxicity. Along with cytogenetic response (CyR), molecular response was assessed with BCR-ABL/ABL ratio. Baseline BCR-ABL gene mutation test was performed. Seventy-one patients (median age, 49.0 years, M:F = 50:21) received escalated dose imatinib. Grade 3 edema in two patients was the only nonhematologic toxicities more than grade 2. For evaluable patients, 30.8% of patients achieved CCyR at 6 months, and median time to treatment failure (TTFx) was 18.0 months. TTFx was longer in patients who achieved greater than 50% reduction in BCR-ABL/ABL within 6 months (early molecular responder (EMR)) compared with those who did not (non-EMR; p < 0.001). Of 31 patients who had mutational status data, three had mutation. All mutants failed to achieve CCyR. In conclusion, escalated dose imatinib shows considerable efficacy with tolerable toxicity in CML patients showing suboptimal response to standard dose imatinib. EMR is an early predictive marker for positive imatinib response.
Koh
Youngil
Y
Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong, Jongno-gu, Seoul 110-744, Republic of Korea.
Kim
Inho
I
Yoon
Sung-Soo
SS
Kim
Byoung Kook
BK
Kim
Dae-Young
DY
Lee
Je-Hwan
JH
Lee
Kyoo-Hyung
KH
Park
Eunkyung
E
Kim
Hyeoung-Joon
HJ
Sohn
Sang Kyun
SK
Joo
Young Don
YD
Kim
Seok Jin
SJ
Chung
Jooseop
J
Shin
Ho-Jin
HJ
Kim
Sung-Hyun
SH
Kim
Chul Soo
CS
Song
Hong Suk
HS
Kim
Min Kyoung
MK
Hyun
Myung Soo
MS
Ahn
Jin Seok
JS
Jung
Chul Won
CW
Park
Seonyang
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000378:metabolism; D001752:Blast Crisis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate
D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl