Why monitoring imatinib in the scope of a study?

TDM currently seems to be a useful approach to optimize CML-treatment:

• Imatinib plasma levels vary considerably between patients under a similar dosage regimen, because of a large inter-individual pharmacokinetics variability of the drug [1].
• Plasma levels, measured at trough, have been shown to correlate with clinical outcome of CML patients (both with respect to response and occurrence of adverse events) [2,3].

Currently, plasma level measurement (TDM) is definitely desirable in case of suboptimal response, experience of severe drug-related adverse events and in patients taking co-medication interfering with imatinib metabolism. It may also allow short-term compliance control.

However it is still unclear:

• Should TDM be performed only in case of occurred clinical problems ("Rescue"-TDM)?
• Or could patients already benefit from a "Routine" TDM, i.e. a systematic elaboration of the best individual dosage regimen on the basis of currently recommended trough plasma concentrations and clinical criteria?

While our laboratory already offers imatinib usual monitoring services for some years (as the Swiss reference laboratory), it is desirable to us, not only to offer this service but also to prospectively evaluate its clinical usefulness and its reasonable utilization.

Therefore we would like to invite all Swiss hematologists to monitor imatinib plasma concentration of their CML patients in the scope of a randomized controlled study, independently of any concerns of the treatment.

References:

1. Widmer N, Decosterd LA, Csajka C et al. Population pharmacokinetics of imatinib and the role of alpha-acid glycoprotein. Br J Clin Pharmacol 2006;62:97-112.

2. Review: Cortes JE, Egorin MJ, Guilhot F, Molimard M, Mahon FX. Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia. Leukemia 2009

3. Further primary literature: Larson et al. Blood 2008; Picard et al. Blood 2007; Singh N et al. Eur J Clin Pharmacol 2009; Widmer N et al. Br J Cancer 2008; Li-Wan-Po et al. Eur J Clin Pharmacol 2010