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Switching between 2nd line TKIs when PCRs plateau

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David Simpson
Topic Author

8 years 2 months ago - 8 years 2 months ago #1123 by David Simpson

Switching between 2nd line TKIs when PCRs plateau was created by David Simpson

I have a 27 yr old with CML initially treated with Imatinib on EPIC study but failed and was changed to dasatinib 100mg daily. He weighs about 130kg.
His PCR’s have plateaued at a warning level. His counts are normal….do I sit tight, increase the dose or change to Nilotinib?
CML; first chronic phase with Hb 87, WCC 434, blasts 17.4, promyelocytes 17.4, basophils 17.4, eosinophils 8.7, platelets 772, spleen 27cm below costal margin; treated with Hydroxyurea from 28 March 2013, EURO 1,612 high risk, SOKAL 2.0 high risk; treated with Imatinib on EPIC study; restaging with a six month bone marrow which showed 100% CML positive cells by FISH, started Dasatinib 25 October 2013

Quantitative RT-PCR analysis for bcr-abl
April 2013 = 177.8% (IS)
Feb 2014 = 7.66% (IS)
May 2014 = 2.04% (IS)
Aug 2014 = 1.45% (IS)
Nov 2014 = 1.12% (IS)
Mar 2015 = 0.840% (IS)
July 2015 = 0.381% (IS)
Sep 2015 = 0.323% (IS)
Oct 2015 = 0.495% (IS)
Feb 2016 = 0.420% (IS)
Aug 2016 = 0.419% (IS)

Last edit: 8 years 2 months ago by Melissa Davis-Bishop.

Tim Hughes
Topic Author

8 years 2 months ago #1124 by Tim Hughes

Replied by Tim Hughes on topic Switching between 2nd line TKIs when PCRs plateau

I guess he is now low risk for progression ( over 3 years out and CCyR ) so the reason to consider switching would be mainly to get him to a TFR attempt some day. He is pretty convincingly in a stable molecular phase or " plateau" at present so you could argue that the more potent TKI nilotinib might improve his molecular response although there is not much clinical evidence to support this. If he was currently on imatinib with this response I would strongly support switching to nilotinib but it is not so clear for a patient currently on dasatinib. Especially when you are considering a young man who may have major drug adherence issues with the twice day fasting regimen required with nilotinib.
The other issue that you raise is a good one - might a higher dose of dasatinib be more effective here, especially considering his weight. Once again, very little data to help here. The randomised study of Dasatinib 100 mg v 140 mg/day didn't show any difference in response but in this specific circumstance there may well be a rationale.
So overall I would not be strongly in favour of switching at this stage but I would give the patient the pros and cons and let him decide.

Beppe Saglio
Topic Author

8 years 2 months ago #1126 by Beppe Saglio

Replied by Beppe Saglio on topic Switching between 2nd line TKIs when PCRs plateau

I agree with Tim, but just an attempt to achieve at least MMR increasing the dose of Dasatinib to 140 mg (70mg BID) can be performed. Indeed it is true that the 034 study did not show a statistical difference between dosages and schedule, but here we were in front of almost an advanced phase, in which the dose has been established to be 140mg. Therefore, in absence of major issues of AEs and tolerance, I would try to increase the dose and to change the schedule, trying to overcome also possible problems of not total adherence to the therapy.

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