Hi, everyone. I just got my kariotype test from 7 mmonths and the result wasn't great. I'm still 40% pH+ so i think i'll havê to chance my tki. I have no mutations and i have some questions:
- if i havê no mutations what could cause my slow response?
- i'm lactose intolerant and know that second generation tki havê lactose. Does it afeccts the drug absorption?
- anybody in my situation out there?
Thanks in advance
Hi Lucas,
You say this result is from a karyotype i.e a cytogenetic test...not a PCR test? I thought your PCR showed a molecular response so I am now confused.
You know you have no mutations so the reason for your slow response to imatinib could be one of several.
Metabolism may be an issue as you say you are lactose intolerant so I assume that means you have some digestive issues? This might affect absorption and it may be that you are not metabolising enough of the drug? Is it possible that you can arrange to have a plasma trough test? You need to maintain a level of at least 1000 ng/ml
Trough imatinib plasma levels are associated with both CCR and MMR to standard-dose imatinib in CML, with a plasma threshold of 1002 ng imatinib/mL
http://www.bloodjournal.org/content/bloodjournal/109/8/3496.full.pdf
and
Plasma trough imatinib levels and molecular response in patients of chronic myeloid leukemia (CML): A single institution study from India.
http://meetinglibrary.asco.org/content/116110-132
There are also studies of the active transport of imatinib which is dependent on the organic cation transporter OCT-1. Patients with low OCT-1 can be identified and may well respond to higher doses of IM or to other TKIs. See following article in Blood Journal:
Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity
http://www.bloodjournal.org/content/110/12/4064.short?sso-checked=true
Re Lactose: as far as I can find out nilotinib and dasatinib contain lactose so you would need to talk with your doctor should either be the choice of an alternative TKI.
Dasatinib contains 135 mg of lactose monohydrate in a 100 mg daily dose and 189 mg of lactose monohydrate in a 140 mg daily dose.
Nilotinib contains lactose and is therefore not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency with a severe degree of intolerance to lactose-containing products or of glucose-galactose malabsorption.
Bosutinib also contains lactose monohydrate.
Hope this is helpful.
Sandy
Hi, sandy, thanks for the insight.
kariotype is my cytogenetic test. My intolerance is not a great problem, it's just moderate. i had 2 PCRs last month from 2 different labs and 2 differents machine. the first one (ipsogen, abl1 control gene) was 2.90% and the second (taqman and bcr control gene) was 6% - big difference but it's in the variation of the test. I don't know if we can measure the plasma levels here. I just received a mail with my results and saying that they will change me to a 2º generation TKI. Both nilotinib and dasatinib have lactose and busotinib is not approved here in brazil. I do have a fast metabolism but i really don't know if it was the reason. Do you know some way to optimize the absorption of the tkis?
actually, i don't i have a less then 10% pcr but did not get to a MCyR even without any mutation. i think next week i'll know what will be my next tki and i'm pretty sure that this time it's gonna work nicely
Hi Lucas,
plasma levels can be affected by the dose- i.e if you have a low trough level then you might respond better by an increased dose. But also- do read the article about OCT 1- high or low. This can be measured and it might be that you have low OCT-1 so that would affect how much of the active TKI is transported directly into the cells- and therefore how effective it is in blocking the protein tyrosine kinase (Bcr-Abl1) that is producing the signal for the cell to continue to divide.
Your doctor can send off a blood sample to the Bordeaux (France) lab for plasma trough level testing. But I am confident that you will respond to a 2G TKI (shame bosutinib is not available).
Sandy
thanks, sandy. Here in brazil we only have 3 TKI avaible (imatinib, dasatinib and nilotinib). Some people aware me about OCT-1 levels in another forum and that nilotinib and dasatinib doesn't use OCT-1 to get inside de cells. I'm confident too, even i never expected a fail early in the treatment.
Cheers!
