Abstract 4284

Introduction

Imatinib (IM), 400 mg/d. induces durable responses in chronic myeloid leukaemia (CML) in chronic phase (CP). However, although IM-biodisponibility is fairly good, its plasma levels are variable and can not be predicted. Recently, these plasma concentrations have been related both to the dose being administrated and to the cytogenetic and molecular responses. Thus, Imatinib pharmacokinetics could be an issue towards treatment optimisation in CML patients. Recent studies suggest that therapeutic IM plasma levels should be above 1040 ng/dl.

Aims

To evaluate the association between IM dose and throughout plasma levels with different clinical outcomes.

Results

In this study, we looked for an association between plasma concentrations and clinical outcomes in 16/86 CML chronic phase patients who did not achieve optimal responses following the European Leukemia Net guidelines (ELN) (table 1). Patients with optimal responses and treated with the same standard doses were also analysed as a control group. Patients receiving doses above 400 mg showed throughout plasma levels considered as appropriate. In 7 of 16 patients (47.5%) not achieving optimal responses (ELN criteria), plasma levels were below the supposed therapeutic ranges. We have found no evidence for a correlation between clinical risk factors at diagnosis and the measurement of optimal plasma levels.

Conclusions

IM plasma levels are well correlated with IM dose administrated in the patients studied. In almost 50% of patients who did not achieve optimal responses, IM plasma levels were under the ranges considered therapeutic. Probably these are the patients who may benefit of a dose increase. Obviously, to learn more about the practical value of these measurements a longer follow up with a larger number of patients is needed.

IMATINIB RESPONSEIMATINIB DOSESIMATINIB PLASMA LEVELS (ng/dl)MUTATIONS
1 SUBOPTIMAL 400 733 NO 
2 SUBOPTIMAL 800 1600 NO 
3 SUBOPTIMAL 400 3490 NO 
4 SUBOPTIMAL 400 853 YES 
5 SUBOPTIMAL 400 2142 NO 
6 SUBOPTIMAL 400 899 NO 
7 SUBOPTIMAL 400 2328 NO 
8 SUBOPTIMAL 400 661 NO 
9 SUBOPTIMAL 400 282 NO 
10 SUBOPTIMAL 400 2208 NO 
11 SUBOPTIMAL 600 1090 NO 
12 SUBOPTIMAL 400 2967 NO 
13 SUBOPTIMAL 400 4221 NO 
14 SUBOPTIMAL 600 1030 NO 
15 SUBOPTIMAL 400 2321 NO 
16 SUBOPTIMAL 400 1469 NO 
IMATINIB RESPONSEIMATINIB DOSESIMATINIB PLASMA LEVELS (ng/dl)MUTATIONS
1 SUBOPTIMAL 400 733 NO 
2 SUBOPTIMAL 800 1600 NO 
3 SUBOPTIMAL 400 3490 NO 
4 SUBOPTIMAL 400 853 YES 
5 SUBOPTIMAL 400 2142 NO 
6 SUBOPTIMAL 400 899 NO 
7 SUBOPTIMAL 400 2328 NO 
8 SUBOPTIMAL 400 661 NO 
9 SUBOPTIMAL 400 282 NO 
10 SUBOPTIMAL 400 2208 NO 
11 SUBOPTIMAL 600 1090 NO 
12 SUBOPTIMAL 400 2967 NO 
13 SUBOPTIMAL 400 4221 NO 
14 SUBOPTIMAL 600 1030 NO 
15 SUBOPTIMAL 400 2321 NO 
16 SUBOPTIMAL 400 1469 NO 
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Disclosures:

No relevant conflicts of interest to declare.

Topics:
imatinib mesylate, leukemia, myelocytic, chronic, plasma, follow-up, leukemia, leukemia, myeloid, chronic-phase, treatment outcome

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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