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Plateued response on second generation TKI

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10 years 4 months ago #923 by joannehickey
Plateued response on second generation TKI was created by joannehickey
I have a 60 year old woman diagnosed chronic phase CML March 2012. She has a history of hypertension only. She started nilotinib April 2012. Within one month she had achieved a CHR but also developed a Grade III transaminitis requiring hold of the drug. This resolved within few weeks and I restarted at reduced dose as per the monograph. She developed recurrent significant transaminitis. I changed to Dasatinib in September 2012. She achieved a complete cytogenetic response by September 2013, however at 18 months (March 2014) she still had not achieved an MMR – BCR-ABL IS of 0.139. Serial measurement shows persistent CCR with most recent BCR-ABL IS of 0.239 (June 2014). Mutational analysis of BCR-ABL is negative. Bone marrow confirms CCR and does not demonstrate any new cytogenetic abnormalities. Her sibs are being typed. She is a very risk averse individual when it comes to therapy and wishes to simply continue to follow along. I had considered increasing the dose of Dasatinib. I am unsure of the role of the newer TKI’s here. I wonder what other’s approach to this situation would be.
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  • Giuseppe Saglio
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10 years 4 months ago #945 by Giuseppe Saglio
Replied by Giuseppe Saglio on topic Plateued response on second generation TKI
The patient showed a slow response to nilotinib therapy, in part due to the onset of toxicity that hampered a correct assumption and finally lead to discontinuation of the initially chosen drug. At the moment, even after switching to Dasatinib, the patient shows a persistent suboptimal response, lacking the achievement of MMR. However for the moment I would not change the therapy as there is no loss of CCyR and therefore no overt failure. For the same reason and due to the age of the patient, I would not consider the option of an alloSCT. I would follow this patient carefully and would check about her compliance to therapy, maybe related to fears related to the previous toxicity .
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  • Jeff Lipton
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10 years 4 months ago #947 by Jeff Lipton
Replied by Jeff Lipton on topic Plateued response on second generation TKI
Agree with Prof Saglio. So long as she has sustained CCyR, would not change. It should be noted as well, that on occasion, some patients exhibit a two phase response and after a plateau in response such as this, a subsequent response improvement after a period of time, even years, can sometimes be observed.
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