Clinical Case Discussion Forum

Subscribe to the Clinical Case Discussion Forum

× To share and enhance best practice management of CML, experts and interested clinicians can discuss difficult or interesting CML cases here. Physicians submit a brief history of the patient and the case for discussion (no more than 200 words) by posting it in this forum ("New Discussion" button below). Please include the country of origin.

Each clinical case will be forwarded to the expert clinical panel for a brief independent response. Consideration should be given to patient confidentiality. Details that are not critical to the case can be changed to preserve anonymity. Please consider including your email with the case. This will not be posted on the website, but is useful should further details be requested by the moderator.

As a full clinical history is necessary for accurate comment, cases and comments on the Forum are ONLY ACCEPTED FROM PHYSICIANS. If individual patients have a specific question we encourage them to contact their healthcare provider. General questions can be emailed to info@cml-foundation.org.

DISCLAIMER: The iCMLf does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this Forum is solely at your own risk.

Managing cardiotoxicity in CML patient on imatinib

Start
Prev
1
Next
End

Jeff Lipton
Topic Author

10 years 9 months ago #735 by Jeff Lipton

Managing cardiotoxicity in CML patient on imatinib was created by Jeff Lipton

I have a dilemma with a patient and would ask for some advice. 43yo man diagnosed about 8 months ago with standard CML-CP low Sokal. Started on Gleevec and has CCyR at 6 months (2log reduction). Background of HLA-B27 ankylosing spondylitis with a pre-Gleevec dilated cardiomyopathy EF 45%. Now about 7 months after starting Gleevec, EF is <35%. Cardiologist feels this is Gleevec related. I am aware of work from MDA in the past describing TK induced LV remodeling. This could very well be Gleevec related. If you think it is, are you aware of whether any of the other TKIs might be better? What would you do?
Thanks for the help.
Jeff

Jorge Cortes
Topic Author

10 years 9 months ago #736 by Jorge Cortes

Replied by Jorge Cortes on topic Re: Managing cardiotoxicity in CML patient on imatinib

This is a difficult one because I think all TKI have a similar potential cardiotoxic effect (myocardial) with imatinib perhaps being the mildest. Thus, I am not sure a change would help. One option is to lower doses (which is always a concern for efficacy, particularly with imatinib) and manage aggressively the heart with close monitoring. If still progressing, maybe a change to bosutinib as it appears to have the least effect (although it could be just a matter of the least follow-up).
I hope this helps.
Best, JC

Michael Mauro
Topic Author

10 years 9 months ago #737 by Michael Mauro

Replied by Michael Mauro on topic Re: Managing cardiotoxicity in CML patient on imatinib

Always hard to truly assess causality in such a case; I think the possibility exists based on a number of basic science papers but I have seen positive as well as negative remodeling effects cited. I will assume it is based on the fact that imatinib was the only new variable and the degree of change.
Then it becomes a choice :
Nilotinib - global vascular disease seems to raise concerns (could compound current CV issues)
Dasatinib - raises concerns about worsening/accelerating the ankylosing spondylitis (AS).
For the record, are we sure the cardiomyopathy is AS related? I thought it cased aortic insufficiency but does it caused dilated myopathy?
Bosutinib might be a very reasonable option.

Tim Hughes
Topic Author

10 years 9 months ago #738 by Tim Hughes

Replied by Tim Hughes on topic Re: Managing cardiotoxicity in CML patient on imatinib

Even though the evidence that imatinib causes cardiac dysfunction is not convincing, it may be relevant for some patients. He may have a specific susceptibility given his other pathology. If imatinib is the cause of his deterioration then he will be in big trouble if you continue it any longer. Therefore you have a difficult choice. Whatever you choose may be equally or more cardio toxic if ABL is the causative target.
Since he is low Sokal and has achieved CCyR, alpha interferon may maintain his response (not sure if this is OK with his ankylosing spondylitis though). If this is not effective or contraindicated I would consider nilotinib, as long as he is not diabetic and has no vascular risk factors. This is most likely to get him to a deep response quickly, giving him a chance of cessation. Bosutinib is also worth considering.

Beppe Saglio
Topic Author

10 years 9 months ago #740 by Beppe Saglio

Replied by Beppe Saglio on topic Re: Managing cardiotoxicity in CML patient on imatinib

I agree with most of the previous comments and suggestions. I want only to add that this is another example of the fact that TKIs able to inhibit the ABL TK activity can be, in particular in specific patients like this one, toxic and sometimes also highly toxic. This, in my opinion, supports the concept that treatment discontinuation should really become the best goal to be achieved in CML therapy as this will probably have a long-term impact on overall survival (a part all the other advantages).

Start
Prev
1
Next
End

Moderators: Nicola, arlene

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