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Questions re Ponatinib and arterial events

  • Harshal Nandurkar
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10 years 3 months ago #726 by Harshal Nandurkar
Questions re Ponatinib and arterial events was created by Harshal Nandurkar
I am aware that ponatinib is associated with 8% arterial thrombotic risk. But could this be reduced by initiating anti-plt or anticoagulant Rx upfront at the time of Ponatinib commencement. What is the global opinion?
I have a 59 y male with T315I mutation. He is from India and continuing on imatinib. The mutant QPCR is slowly rising but still it seems that the sensitive clone is dominant and the patient is in morphological remission.
He has access to ponatinib supported by the Indian government.
Is homoharringotonine easily available and a reasonable alternative? The patient has 5 sibs and donor search is planned.
  • Tim Hughes
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10 years 3 months ago #727 by Tim Hughes
Replied by Tim Hughes on topic Re: Questions re Ponatinib and arterial events
The incidence of arterial events is probably higher than 8% (see attached slides from my ASH Education talk). The risk seems quite low in patients with no risk factors - but they aren't that common. Risk is very high in diabetics and patients with previous vascular events. There is some modelling by Ariad that suggests that lower doses substantially reduce the risk. No evidence yet regarding antiplatelet agents or anticoagulants. Patients who were on aspirin in the PACE trial had a high incidence of events - but they were presumably a high risk group because they were taking aspirin for a reason. If your patient is rising above 1% BCR-ABL then he is probably deriving a limited benefit from imatinib. Your options are (with my personal opinion included - not always evidence based):

Omacetaxine - very few patients achieve molecular responses, I don't see much of an advantage over hydroxyurea.

Ponatinib - perhaps use at low dose (start with 15 mg/day) and see if you can achieve a molecular response. Probably don't go higher than 30 mg/day. Concomitant aspirin and aggressive measures to reduce risk (esp hypertension) seems a reasonable bet at this stage. I would probably avoid if he is diabetic or has had previous vascular events.

Allograft - only if you can't achieve molecular response on modified dose ponatinib.
  • Jorge Cortes
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10 years 3 months ago #728 by Jorge Cortes
Replied by Jorge Cortes on topic Re: Questions re Ponatinib and arterial events
With longer follow-up the incidence has increased to around 10-15%. Baseline risk factors increase the risk of having such events. The role of anti-pletelt agents is not well known but my guess is that they will help at least some patients. On patients with the proper indication (such as those with T315I) ponatinib is still the best option available. I would use it and monitor the patient closely. This includes monitoring blood pressure and controlling if elevated, as well as managing any other co-morbidities (e.g., diabetes,m colesterol, etc) and paying particular attention to healthy lifestyle (excercise, adequate diet, etc.).
Omactexanine is useful in these patients but I would use after ponatinib as the rate of response is greater with ponatinib.
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10 years 3 months ago #729 by gsaglio
I agree with Dr Hughes: 30 mg of ponatinib, managing risk factors when possible. Once that a good molecular response is achieved maybe it is wise to lower the dose to a maintainance one (15 mg) and maybe try to associate a small dosage of Peg-IFN once a week.
Allograft at 59 y only if no disease control and depending on the risk profile of the patient.
  • Jeff Lipton
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10 years 3 months ago #730 by Jeff Lipton
Replied by Jeff Lipton on topic Re: Questions re Ponatinib and arterial events
Although I agree with what has been said in regard to ponatinib, it is as mentioned, a risk benefit issue. A careful medical history may tell you which patients are at risk. The prophylactic suggestions are reasonable and make common sense, but we really have no evidence to prove that these will prevent or reduce the incidence of vascular events. A decision to use ponatinib should be made after carefull review of risk, likely starting at a lower dose as Tim suggests, and very careful monitoring for adverse events. I do disagree somewhat that omacetaxine has a limited role. Although it is technically more difficult to administer, there are positive and durable results in t315i mutations (I have one out now at more than 5 years) and should not be taken off the table as an option. As an allo-transplanter as well, consideration of this as an option if a good donor is available and the patient is healthy, must also remain as a choice. It is still a very viable and effective approach, and should not be reserved for when the patient shows evidence of disease progression. I would identify a donor if available, and if one of the previous drug options is chosen first, even though this can be the next alternative, be prepared to move to this modality sooner rather than later, if they are ineffective or toxic.
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