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Max. showing the last 6 posts - (Last post first)
I agree with David. Given his high risk of relapse, his positive BCR-ABL result and his low risk of vascular events, I would be very reluctant to reduce the ponatinib dose at this stage. I doubt the ponatinib is the cause of his transient cardiac dysfunction. Hopefully he will heed your advice to proceed with an allograft – especially if he is still PCR positive in the marrow after cycle 6.
Tim Hughes
ORIGINAL CASE:
I would appreciate your advice with regards to a young CML patient on dasatinib who progressed to blast phase ALL last year.
I commenced him on ponatinib 45mg daily from July 2018 in conjunction with hyperCVAD therapy. He has been responding well and has now completed 7 of 8 cycles of HyperCVAD. His BCR-ABL transcript levels have fallen as follows
4/7 250% PB 330% BM
10/9 0.0055% PB
13/9 0.0037% BM
30/10 0.0015% PB
Latest result pending.
He has completed 7 cycles of Hyper CVAD and is due to commence his final cycle in early January. He also had a positive LP mid way through treatment in September and has completed full CNS treatment with subsequent clear samples. He was quite unwell with neutropenic sepsis in cycle 6 and his cardiac function declined dramatically. I did not know if this was due to sepsis or if the ponatinib or doxorubicin could be implicated. He was commenced on cardiac remodeling drugs, sepsis resolved and a follow up ECHO demonstrated marked improved so I pushed ahead with cycle 7 and ponatinib at the same dose of 45mg. I have been going over the PACE trial data and it suggests that I should consider decreasing the dose of the ponatinib due to the increased risk of side effects if he has attained a good molecular response which he has. He has decided against transplant so my concern is that the ponatinib is the only thing at present keeping him from relapsing – should I decrease to 30mg. The other thing of note is that his disease was not resistant to dasatinib – he finally acknowledged that he had stopped taking the dasatinib which led to his progression to blast crisis.
It's concerning that even with a combination approach, MRD is still detectable. On the PACE study, the median progression free survival with ponatinib monotherapy for CML-BC was ~4mos. I worry that the risk of relapse is high once a patient finishes chemo. I understand that non-adherence may have contributed to disease progression, though this does not imply a better prognosis - the horse has bolted...
There is no good evidence to guide us on the optimal dose of ponatinib for maintenance, especially for CML-BC. However, the general advice is that for medium to long term ponatinib use, dose de-escalation should be considered once a response is achieved. This is in keeping with your thoughts. Again, this was a conclusion extrapolated from post hoc analyses, and I'm not sure to what extent this is applicable for advance phase disease.
David Yeung
I would appreciate your advice with regards to a young CML patient on dasatinib who progressed to blast phase ALL last year.
I commenced him on ponatinib 45mg daily from July 2018 in conjunction with hyperCVAD therapy. He has been responding well and has now completed 7 of 8 cycles of HyperCVAD. His BCR-ABL transcript levels have fallen as follows
4/7 250% PB 330% BM
10/9 0.0055% PB
13/9 0.0037% BM
30/10 0.0015% PB
Latest result pending.
He has completed 7 cycles of Hyper CVAD and is due to commence his final cycle. He also had a positive LP mid way through treatment in September and has completed full CNS treatment with subsequent clear samples. He was quite unwell with neutropenic sepsis in cycle 6 and his cardiac function declined dramatically. I did not know if this was due to sepsis or if the ponatinib or doxorubicin could be implicated. He was commenced on cardiac remodeling drugs, sepsis resolved and a follow up ECHO demonstrated marked improved so I pushed ahead with cycle 7 and ponatinib at the same dose of 45mg. I have been going over the PACE trial data and it suggests that I should consider decreasing the dose of the ponatinib due to the increased risk of side effects if he has attained a good molecular response which he has. He has decided against transplant so my concern is that the ponatinib is the only thing at present keeping him from relapsing – should I decrease to 30mg. The other thing of note is that his disease was not resistant to dasatinib – he finally acknowledged that he had stopped taking the dasatinib which led to his progression to blast crisis.
Any advice would be greatly appreciated.
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Copyright © 2023 All Rights Reserved. The iCMLf is registered as charity no. 1132984 in England and Wales
Registered Address: International CML Foundation - 20 Eversley Road - Bexhill-On-Sea, East Sussex, TN40 1HE - UK
This website uses cookies to manage authentication, navigation, and other functions. By using our website, you agree that we can place these types of cookies on your device.View our Privacy Policy
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