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On April 21, 2010, the U.S. Food and Drug Administration (FDA) issued a warning letter to Novartis criticizing its promotion of blood level testing on its CML and GIST Alliance websites. As of September 30, 2010, Novartis terminated the CML and GIST Alliance programs which it had contracted with TDM Pharmaceutical Research, LLC. Since then, the Life Raft Group has been working tirelessly behind the scenes to try and resume this critical testing procedure as it has important potential for managing GIST patient care.
At this time, due to perceived potential conflict of interest, Novartis will not review its financial support for blood level testing.
Despite the termination of Novartis support, Dr. Linyee Shum, the Executive Director and Chief Scientific Officer of TDM Pharmaceutical Research has graciously offered to continue to provide blood level testing to the GIST patient population. The target date for resumption of testing is May 16, 2011.
Because there is no longer any Novartis funding support for testing, TDM will bill the patients insurance for reimbursement. If insurance does not cover the procedure, TDM has agreed to a sixmonth trial period in which they will cover the costs of testing for Life Raft Group members. The supplies needed to collect samples are readily available in most oncology offices, however sample collection kits are available from TDM if needed.
In order to get testing through TDM Pharmaceutical Research, your physician may contact 1-866-990-0007 firstname.lastname@example.org. Contacting TDM in advance is recommended so they can go over the logistics of submitting a sample.
Why do plasma testing?
The amount of Gleevec absorbed by patients can vary widely between patients. For patients taking 400 mg of Gleevec, some will have a high concentration of Gleevec in the blood and some will have a low concentration. Plasma testing measures the actual concentration of Gleevec in the plasma (a part of blood) of a patient. Emerging evidence suggests that some GIST and CML patients may not have concentrations that are adequate to ensure a long-term response to Gleevec.
There are several reasons for doing plasma testing. Measuring imatinib plasma levels may identify patients that are not taking their imatinib on a regular basis. This is a significant problem (affecting 25% or more of patients) and several reports have identified poor adherence as a predictor of imatinib failure in CML. Monitoring imatinib plasma levels may also help evaluate cases of apparent imatinib toxicity. For example, in a patient taking 400 mg of imatinib with intolerable side-effects, plasma testing might confirm high imatinib levels as the reason for the toxicity. In the case of a dose reduction, a second plasma test might give some reassurance of adequate imatinib levels even though the dose may be below 400 mg.
In addition to studying patient compliance, plasma level testing may help prevent resistance. In 2009, Dr. George Demetri and colleagues reported in The Journal of Clinical Oncology that imatinib plasma levels are linked to clinical benefit in patients with unresecmetastatic GISTs. Demetri and colleagues evaluated plasma data from GIST patients in the original imatinib phase II trial, in which the authors concluded that “preliminary analysis suggests that a low (steady state) plasma level of imatinib (i.e. 1,100 ng/mL) might contribute to drug failure in patients with advanced GIST …we found that patients with a low plasma exposure (Cmin less than 1,100 ng/mL) showed a trend of low rate of objective response and rapid evolution of resistance (short time to progression). These results suggest that a minimal plasma threshold may be necessary to achieve and maintain clinical response. This hypothesis is best supported in patients with KIT exon 11 mutations, who exhibited improved clinical outcomes with imatinib trough levels more than 1,110 ng/mL.” Furthermore, Demetri and colleagues state “in patients with advanced GIST, imatinib trough levels at steady state were associated with clinical benefit. Patients with imatinib Cmin (trough level) below 1,100 ng/mL showed a shorter time to progression and lower rate of clinical benefit (OOBR). Further studies are justified to test whether monitoring IM plasma levels might optimize clinical outcomes for patients with GIST”.
If you have questions about this procedure, please contact The Life Raft Group (1-973-837-9092).
Samples should be sent to the following address:
TDM Pharmaceutical Research, LLC
100 Biddle Ave Suite 202
Newark, DE 19702
The Life Raft Group would like to extend special thanks to Dr. Shum for his efforts and generosity. To learn more about the man behind the testing, a profile on Dr. Shum will be published in the June 2011 newsletter.