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Dastatinib after imatinib resistance

According to Professor Jane Apperley at the video below, a patient who encounters imatinib resistance has a 50% chance of a suitable response to a second-generation TKI. In the event of repeated resistance then the patient has a 25% chance of responding to a second second-generation TKI. 

https://cmlsupport.org.uk/article/uk-chronic-myeloid-leukaemia-patient-d...

In my case, I achieved a complete cytogenetic response at 11 months but failed to achieve a major molecular response at 18 months on imatinib. My BCR-ABL1 is plateaued at 0.5% at the last result. A local laboratory generic test indicated zero mutations but I am awaiting results from  the Kings next generation sequencing trial. 

I have been moved onto dasatinib. Is it correct that my chance of success on dasatinib is as little as 50%?

 

 

I applaud your scientific delving.  Anecdotally, however, it APPEARS that people who are slow on Gleevec respond very well to Sprycel.  My profile on Gleevec mirrored yours; as soon as I switched to Sprycel my PCR plunged, zoomed downward.  I whomped the MMR and zipped down to a nice zero to the right very fast.  Now have a steady two-zero "plateau."  You can overthink this - just try it and see what happens?

Thank you, kat 73, for your reassurance. I was becoming somewhat disheartened following my Googling and search for relevant statistics. I did momentarily reach 0.15% (just short of MMR) but then I returned to the 0.5% plateau within six weeks. I will not know what happens next until I have the next blood sample taken in three months' time and then wait another one and a half months for the results.

On the positive side, I think that after one week on dasatinib I actually feel healthier. I know it is early days.

This is a completely data-less consideration, but I wonder if those who had a resistance to dasatinib as well as imatinib did so at a higher PCR than yours - which of course is within touching distance of MMR. 

We didn’t wait out to see if imatinib would plateau for me. I was responding, but slowly, and side effects included necessitated a move to dasatinib. I’m at MR5 these days but I’m sure that’ll bounce up and down again over time.

David.

 

Thank you, David, for your extra reassurance. I have seen data representing the cohort that has achieved the complete cytogenetic response but not the major molecular response. However, I am inclined to agree with your supposition. The data sample is probably too small to factor in the different risk factors. My consultant did tell me that in prior times she would have increased my imatinib dosage but that the change of TKI is the better decision and the time is right to do so.

Your experience raises my confidence.

We are not expecting the results from the Kings next generation sequencing trial for mutations to indicate the presence of mutation but we will wait and see.

Glad you feel better on dasatinib.  I'll add to my anecdotal observance that people who feel dreadful on imatinib often feel much better on dasatinib.  Feeling (and looking!) horrible were my reasons for switching and improvement was pretty quick and dramatic.  Others have not had this experience, though, of course.  I think it all depends on the differing "mixes" of CML we all have as individuals.