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Losing molecular response to multiple TKI without any KD mutation

  • Prof. Akhil Ranjon Biswas
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3 days 17 hours ago - 1 day 21 hours ago #2019 by Prof. Akhil Ranjon Biswas
Losing molecular response to multiple TKI without any KD mutation was created by Prof. Akhil Ranjon Biswas
From Bangladesh

A 29-year-old young man, whose CML risk status was not documented before initiation of treatment, consulted me while he was taking Imatinib for 2 months. He was in CHR at that time and achieved MMR at 3 months. However, he lost MMR at 12 month and loss of MMR was confirmed at 15 month. His KD mutation at that time came negative and his TKI was changed to Dasatinib.

He tolerated dasatinib very well and he achieved deep MR (MR 4.5) at 7 months of dasatinib. But at 11 months he lost his deep MR having BCR-ABL1 in IS 0.0606. I'm planning to repeat his q-PCR after 1-2 months.

Is it likely to be a BCR-ABL1 independent resistance to TKI? If so, should he proceed for allogenic stem cell transplantation now? or wait for further decision till loss of MMR? Should I try 3rd TKI now or after loss of MMR? Any combination with TKI can help? Should I check KD mutation once again?
Last edit: 1 day 21 hours ago by arlene.
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  • Gianantonio Rosti
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1 day 21 hours ago - 1 day 21 hours ago #2020 by Gianantonio Rosti
Replied by Gianantonio Rosti on topic Losing molecular response to multiple TKI without any KD mutation
Firstly, there is no indication to repeat mutational analysis (in condition of MMR, the chance of finding a mutation is very, very low, null; not due to lack of sensitivity but because it is quite unlikely to find a mutation in MMR).

Secondly, the disease is quite sensitive to TKI treatment and the current ‘loss of DMR’ should be interpreted as an expected oscillation of the molecular level.

So, I suggest to go on with Dasatinib, next QPCR at 3-4 months after the previous one.

Hope this will help , I remain of course available for further interactions.
Last edit: 1 day 21 hours ago by arlene.
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