Cardiac side effects from drugs: Predictable?

[ThreeWs]

Hi All,

Some of our therapy drugs i.e. Rituxan & Ibrutinib, have been associated with cardiac side effects for some patients. It would be interesting to know how sensitive this simulated heart model would be in testing CLL drugs. Not only is CLL expressed very differently - almost uniquely in each patient, but there appears to be a serious lack of knowledge or techniques to predict how well or poorly any individual might respond to a given drug. I suspect that this model is not the ultimate say as to who might develop A-Fib or arrhythmias on Ibrutinib or any other CLL therapeutic but it is a step in the right direction for pre-initiation of therapy testing to determine many damaging side effects of the drugs meant to help us. This model is a good sign that we might hope to see this type of technology become a part of individualized medicine in the future.

pharmaceutical-journal.com/...

We all have unique vulnerabilities, think of tendon rupture with fluoroquinolone antibiotics, that can disable a subset of patients yet that class of antibiotic can be a lifesaver for a majority of patients. Wouldn’t it be great to know ahead of time which side of the fence you are on before being given a drug?

WWW

[manzelka]

I found this of interest as two years ago my husband had Tacot Subo's cardiomyopathy after two lots of FCR, but had no reaction to bendamustin + rituximab.

[june65]

My husband had Retuximab, cyclophosamide and fludarabine to treat his CLL five years ago and following the six treatments he developed heart failure. He went to see a heart specialist in Broad Green hospital in Liverpool who said the only thing that could have caused the amount of damage to his heart would have been a massive heart attack, and as he had not had a heart attack the only other thing could be the chemotherapy. He has recently been told he has to have treatment again, he had one round of the same chemo drugs (without the Retuximab) his haemotolgist does not believe that the chemo could do this damage, and ended up rushed into hospital last week with a very bad chest infection. Does anyone have any advise regarding his treatment as we just go with what his haematologist suggests and hope for the best, but it is a terrible worry.

[AussieNeil Administrator in reply to june65]

Has your husband's haematologist looked into your husband's eligibility for a clinical trial? I wouldn't think that he is likely to get a very lengthy remission on just FC after completing a full course of FCR 5 years ago. What reason was given for omitting the Rituximab?

In your situation, I'd seriously consider asking for a second opinion elsewhere.

Neil

[Cllcanada Top Poster CURE Hero in reply to AussieNeil]

All the nitrogen mustard treatments, like cyclophosphamide and bendamustine have some rare cardiotoxicity.

Rituxan has been shown to have rare cardiotoxicity, as well.

You should seek a second opinion as Neil suggests...

[june65]

Thanks both for those useful replies. I will definitely look into getting a second opinion, but wonder how long this will take, here in the U.K things don't move that quickly .

[june65]

AussieNeil. Forgot to say, the reason for not giving Rituximab was that his white blood count was too high, it was 200.

[AussieNeil Administrator in reply to june65]

Not using Rituximab didn't sound right to me, so I checked with Cllcanada who has lived the experience and he advised that Rituximab will likely be withheld until your husband's lymphocyte blood count has fallen low enough and allopurinol will be given to protect against Tumour Lysis Syndrome. Check with your husband's doctor to confirm that you husband will eventually get FCR (added Rituximab) when his tumour burden has fallen to safe levels from the FC treatment. With Rituxtimab, he should get a deeper and longer lasting remission.

Neil

[ThreeWs in reply to AussieNeil]

I don't know about FCR but Dr. Byrd, CLL specialist at OSU Medical Center has written that concurrent use of F with R produces a better response than a sequential use. This was with frontline TX and he does not recommend FR with all patients so that may be a factor in the research result. Use of all our drugs may prominently figure in how well we respond.

bloodjournal.org/content/10...

WWW

[june65 in reply to AussieNeil]

Thanks Neil, you're very kind going to so much trouble to help. My husband was supposed to have another apt with his haematologist this morning but is unable to go as he has been very poorly with an upper respitory tract infection, so he is going next week. I am also looking into getting a second opinion. I will keep you informed.

Many thanks

June

[june65]

Neil. My husband went for his apt with his haematologist yesterday, she said his WBC had come down from 200 to 50, his haemoglobin was good but his platelets had dropped from 62 to 13, we had to go back yesterday evening for a bag of platelets. He has to go back on Tuesday for another blood test and depending on the results of that he may need another bag of platelets. But the good news is he is being referred to Dr Adrian Bloor at Christies hospital in Manchester for a second opinion before he has any more treatment.

[AussieNeil Administrator in reply to june65]

Thanks for the update June. It's good to hear that you are getting a second opinion with a renown CLL expert at Christies. I hope your husband's platelets quickly recover.

Neil