All About Gleevec (Glivec)

This report is based on analysis of the pharmacokinetic data from the original phase II Gleevec trial for GIST (B2222), which started in July of 2000. Plasma levels (plasma is one component of blood) taken after 29 days of Gleevec, were available for 73 of the 147 patients enrolled in the trial. These plasma levels were grouped into quartiles according to imatinib trough plasma concentrations (the level of drug in the blood at its lowest point during the day, just before taking the daily Gleevec capsule).The plasma levels and response rates of these groups are listed in the table below.

Plasma levels and response rates

The authors concluded that, “Exposure to adequate drug levels of imatinib appears to correlate with clinical benefit; patients with the lowest imatinib levels show lowest objective response and shortest time to progression. These results suggest that monitoring pharmacokinetic/ pharmacodynamic relationships may provide novel predictive markers and that exposure to adequate IM trough plasma concentrations (>1,110 ng/mL) is important for optimal clinical response.”

A video report is available on the medpageTODAY website. In the interview, Dr. Demetri explained that “when you give Gleevec or any other kinase inhibitor to a group of patients, they will handle it very differently, some people will have high levels and some people will have low levels… The important part about that is whether we for years might be underdosing people, and whether we perhaps should develop a blood test to check the levels of this drug in people’s blood and have more certainty that there’s actually therapeutic levels in the blood.” Demetri went on to explain that “it’s possible that we could have done this analysis and found nothing at all, but in fact, we saw something that is a bit worrisome for the patients with the lowest levels of the drug.” The next step according to Demetri will be to “… talk with our colleagues, decide exactly how much this is worth pursuing, (and) decide how to mount a large trial.”

Blood Level Testing

Patients can request testing of imatinib blood levels. Determining an optimum imatinib blood level will probably require a well designed clinical trial that examines multiple factors. For now, the best information (Demetri et al. 2008 GI ASCO) we have is preliminary and suggests that trough imatinib plasma levels should be above 1,100 ng/ml (see above). Testing imatinib blood levels is currently available for GIST patients.

A new program called GIST Alliance was launched at the end of 2008 by Novartis as a unique support program designed to help healthcare professionals optimize outcomes in KIT+ GIST patients. Healthcare professionals can learn more about available resources to help achieve optimal outcomes for GIST patients.

Within the site, you will find information about blood level testing for GIST. GIST Alliance connects you with Avantix Laboratories to perform the test. For more information, see http://www.cmlalliancebloodleveltesting.com/. Through Avantix, your doctor can order optional free testing kits, send plasma samples for analysis, and view tests results online. This is the fastest way to receive information. It also allows physicians to easily view patients' full test-result histories all at once.

A program called CML Alliance also exists. This program offers blood level testing for CML patients in different countries. GIST patients outside the U.S. may be eligible for particiption through this program. Programs that we are aware of will be listed below.

Helpful Sites

Plasma level testing: what we know, what we don't & what we hope to learn

Is there a role for drug level testing?

Routine mutational and plasma level testing: the time has come

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References

1. Correlation of imatinib plasma levels with clinical benefit in patients (Pts) with unresectable/metastatic gastrointestinal stromal tumors (GIST)
G. D. Demetri, Y. Wang, E. Wehrle, C. Blanke, H. Joensuu, M. von Mehren